Application of protein composition in early diagnosis of lung cancer

Abstract

The invention discloses application of a protein composition in early diagnosis of lung cancer, and belongs to the technical field of biological medicines. The protein composition comprises the newly screened antigen protein FAM104B, the antigen protein can be used for detecting the IgG antibody of the lung cancer in serum, so that the protein composition is used for early diagnosis of the lung cancer, the sensitivity is 48%, the specificity is 95%, the average value of the sensitivity and the specificity is 71%, and the sensitivity and the specificity are higher than those of a single antigen protein in the prior art. Meanwhile, the antigen protein is combined with other antigen proteins to detect the IgG antibody of the lung cancer in serum, so that the antigen protein is used for early diagnosis of the lung cancer, the average value of the sensitivity and the specificity of the antigen protein is 70%-88%, particularly, the average value of the sensitivity and the specificity of a protein composition containing the antigen proteins FAM104B and RND3 is greater than 78%, and the accuracy of early diagnosis of the lung cancer is improved.

Description

Technical Field

[0001] The present application belongs to the field of biomedicine technology, and specifically relates to the application of a protein composition in the early diagnosis of lung cancer. Background Art

[0002] Lung cancer is one of the malignant tumors with the highest morbidity and mortality rates worldwide. The prognosis of lung cancer is closely related to its development stage. The five-year survival rate of localized lung cancer is 53%, while the five-year survival rate is only 4% when metastasis occurs. Therefore, early screening and early diagnosis of lung cancer have become the key to prolonging the survival of patients and saving their lives. Early detection and timely prevention and treatment of lung cancer can significantly improve the survival rate and quality of life of patients.

[0003] Early diagnosis of lung cancer mainly includes imaging examinations and biomarker examinations. Biomarkers include lung cancer markers (lung cancer antigens), circulating tumor cells (CTCs), epigenetics (such as DNA methylation), ctDNA and other blood components, tumor-related antigen autoantibodies, etc. Since the production of autoantibodies is a humoral immune response of the immune system to tumor-related antigens, the level of autoantibodies in serum is much higher than the conventional antigen level. In addition, due to the high specificity and sensitivity of the antigen-antibody reaction, autoantibodies are easier to detect accurately than other markers even in the presence of a large amount of albumin interference in the serum. In other words, tumor autoantibodies are easier to detect than corresponding tumor antigens. Therefore, early diagnosis of lung cancer by detecting lung cancer autoantibodies has a broader prospect.

[0004] In the related art, for example, the Chinese invention patent with publication number CN110456062A records the use of SNX9 autoantibody detection reagent in the preparation of a lung cancer screening kit, with a sensitivity of 24.1%, a specificity of 93.1%, and an average of sensitivity and specificity of 58.6%. Another example is the Chinese invention patent with publication number CN116482365A previously applied for by the applicant, which records a protein composition of any one or more of the antigen proteins XAGE1A, RBPJ and CEACAM5, and antigen proteins TP53, NSG1, MAGEC2, SULT2B1, DDSNX9, NUDT14, PGK1 and KRT19. The protein composition detects lung cancer autoantibodies in serum, thereby being used for early diagnosis of lung cancer, with a sensitivity of 45% to 86%, a specificity of 84% to 100%, and an average of sensitivity and specificity (Discriminative ability) of 72 to 86%.

[0005] The selection of antigen proteins, including the type and quantity of antigen proteins, significantly affects the sensitivity and specificity of early diagnosis of lung cancer. Finding antigen proteins or antigen protein combinations with sensitivity, specificity, or both sensitivity and specificity, to detect lung cancer autologous IgG antibodies in serum for early diagnosis of lung cancer has always been a hot issue in early diagnosis of lung cancer. Summary of the invention

[0006] 1. Purpose of the Invention

[0007] The purpose of the present application is to provide an application of a protein composition in the early diagnosis of lung cancer. The antigen protein or its composition screened in the present application can detect lung cancer autologous IgG antibodies in serum, thereby being used for the early diagnosis of lung cancer.

[0008] 2. Technical solution

[0009] In order to solve the above problems, the technical solutions adopted in this application are as follows:

[0010] The present application provides the use of antigen protein FAM104B in the preparation of a product for early diagnosis of lung cancer. The diagnostic product utilizes the antigen protein FAM104B to detect lung cancer autologous IgG antibodies in serum for early diagnosis of lung cancer. The sensitivity is 48%, the specificity is 95%, and the average value of the sensitivity and specificity is 71%, which are basically the same as the average values ​​of the sensitivity, specificity, and sensitivity and specificity of a single antigen protein in the prior art, or even better.

[0011] The present application also provides the use of antigen protein RND3 in the preparation of a product for the early diagnosis of lung cancer. The diagnostic product uses the antigen protein RND3 to detect lung cancer autologous IgG antibodies in serum for early diagnosis of lung cancer. Its sensitivity is 29%, specificity is 95%, and the average value of sensitivity and specificity is 62%, which is basically the same as the average value of sensitivity, specificity, and sensitivity and specificity of a single antigen protein in the prior art, or even better.

[0012] The present application also provides the use of the antigen protein CCDC9 in the preparation of a product for the early diagnosis of lung cancer. The diagnostic product uses the antigen protein RND3 to detect lung cancer autologous IgG antibodies in serum for early diagnosis of lung cancer. The sensitivity is 28%, the specificity is 95%, and the average value of the sensitivity and specificity is 61%, which is basically the same as the average value of the sensitivity, specificity, and sensitivity and specificity of a single antigen protein in the prior art, or even better.

[0013] The present application also provides the use of the antigen protein PDIK1L in the preparation of a product for the early diagnosis of lung cancer. The diagnostic product uses the antigen protein PDIK1L to detect lung cancer autologous IgG antibodies in serum for early diagnosis of lung cancer. The sensitivity is 23%, the specificity is 95%, and the average value of the sensitivity and specificity is 59%, which are basically the same as the average values ​​of the sensitivity, specificity, and sensitivity and specificity of a single antigen protein in the prior art, or even better.

[0014] The present application also provides the use of the antigen protein YWHAZ in the preparation of a product for the early diagnosis of lung cancer. The diagnostic product uses the antigen protein YWHAZ to detect lung cancer autologous IgG antibodies in serum for early diagnosis of lung cancer. The sensitivity is 18%, the specificity is 95%, and the average value of the sensitivity and specificity is 56%, which are basically the same as the average values ​​of the sensitivity, specificity, and sensitivity and specificity of a single antigen protein in the prior art, or even better.

[0015] The present application also provides the use of a protein composition in the preparation of a product for early diagnosis of lung cancer, the product comprising a protein composition, the protein composition comprising antigenic proteins FAM104B and RND3, the diagnostic product using the protein composition to detect lung cancer auto-IgG antibodies in serum, thereby being used for early diagnosis of lung cancer. The antigenic protein SNX9 in the present application is recorded in a Chinese invention patent with a publication number of CN110456062A and the invention name of the use of SNX9 autoantibody detection reagent in the preparation of a lung cancer screening kit, however, the sensitivity of the antigenic proteins FAM104B and RND3 is 65%, the specificity is 95%, and the mean is 80%, which is slightly higher than the sensitivity (63%), specificity (95%), and mean (79%) of the antigenic proteins FAM104B and SNX9.

[0016] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and RND3, and also includes any one or more of the antigenic proteins SNX9, CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0017] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and RND3, and also includes any one of antigenic proteins SNX9, CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0018] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein SNX9.

[0019] Furthermore, the above protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein TTC1.

[0020] Furthermore, the above protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein MAGEA8.

[0021] Furthermore, the above protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein PDIK1L.

[0022] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein CCDC9.

[0023] Furthermore, the above protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein YWHAZ.

[0024] Furthermore, the above protein composition includes antigenic proteins FAM104B and RND3, and also includes antigenic protein ACPP.

[0025] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes any one or more of antigenic proteins CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0026] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes any one of antigenic proteins CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0027] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes antigenic protein TTC1.

[0028] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes antigenic protein MAGEA8.

[0029] Furthermore, the above protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes antigenic protein PDIK1L.

[0030] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes antigenic protein CCDC9.

[0031] Furthermore, the above protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes antigenic protein YWHAZ.

[0032] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes antigenic protein ACPP.

[0033] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B, RND3, MAGEA8, and also includes any one or more of the antigenic proteins SNX9, CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

[0034] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and also includes any one of antigenic proteins SNX9, CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

[0035] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and antigenic protein TTC1.

[0036] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and antigenic protein SNX9.

[0037] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and antigenic protein CCDC9.

[0038] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and antigenic protein PDIK1L.

[0039] Furthermore, the above protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and antigenic protein YWHAZ.

[0040] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and antigenic protein ACPP.

[0041] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes any one or more of antigenic proteins CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

[0042] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes any one of antigenic proteins CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

[0043] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes antigenic protein TTC1.

[0044] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes antigenic protein PDIK1L.

[0045] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes antigenic protein CCDC9.

[0046] Furthermore, the above protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes antigenic protein YWHAZ.

[0047] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes antigenic protein ACPP.

[0048] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes any one or more of antigenic proteins CCDC9, PDIK1L, YWHAZ and ACPP.

[0049] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes any one of antigenic proteins CCDC9, PDIK1L, YWHAZ and ACPP.

[0050] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes antigenic protein CCDC9.

[0051] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes antigenic protein PDIK1L.

[0052] Furthermore, the above protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes antigenic protein YWHAZ.

[0053] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes antigenic protein ACPP.

[0054] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, TTC1 and MAGEA8, and also includes any one or more of antigenic proteins PDIK1L, YWHAZ and ACPP.

[0055] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, TTC1 and MAGEA8, and also includes any one of antigenic proteins PDIK1L, YWHAZ and ACPP.

[0056] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, TTC1 and MAGEA8, and also includes antigenic protein PDIK1L.

[0057] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, TTC1 and MAGEA8, and also includes antigenic protein YWHAZ.

[0058] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, TTC1 and MAGEA8, and also includes antigenic protein ACPP.

[0059] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, PDIK1L, TTC1 and MAGEA8, and also includes antigenic proteins YWHAZ and / or ACPP.

[0060] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, PDIK1L, TTC1 and MAGEA8, and also includes antigenic protein YWHAZ.

[0061] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, PDIK1L, TTC1 and MAGEA8, and also includes antigenic protein ACPP.

[0062] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, PDIK1L, TTC1 and MAGEA8, and also includes antigenic proteins YWHAZ and ACPP.

[0063] The present application provides an application of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and SNX9. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0064] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and SNX9, and also includes any one or more of antigenic proteins RND3, CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0065] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and SNX9, and also includes any one of antigenic proteins RND3, CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0066] The present application provides an application of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and CCDC9. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0067] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and CCDC9, and also includes any one or more of the antigenic proteins SNX9, RND3, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0068] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and CCDC9, and also includes any one of the antigenic proteins SNX9, RND3, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

[0069] The present application provides an application of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and PDIK1L. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0070] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and PDIK1L, and also includes any one or more of antigenic proteins SNX9, RND3, CCDC9, YWHAZ, TTC1, MAGEA8 and ACPP.

[0071] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and PDIK1L, and also includes any one of the antigenic proteins SNX9, RND3, CCDC9, YWHAZ, TTC1, MAGEA8 and ACPP.

[0072] The present application provides an application of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and YWHAZ. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0073] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and YWHAZ, and also includes any one or more of the antigenic proteins SNX9, RND3, CCDC9, PDIK1L, TTC1, MAGEA8 and ACPP.

[0074] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and YWHAZ, and also includes any one of the antigenic proteins SNX9, RND3, CCDC9, PDIK1L, TTC1, MAGEA8 and ACPP.

[0075] The present application provides an application of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and TTC1. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0076] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and TTC1, and also includes any one or more of the antigenic proteins SNX9, RND3, CCDC9, PDIK1L, YWHAZ, MAGEA8 and ACPP.

[0077] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and TTC1, and also includes any one of the antigenic proteins SNX9, RND3, CCDC9, PDIK1L, YWHAZ, MAGEA8 and ACPP.

[0078] The present application provides the use of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and MAGEA8. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0079] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and MAGEA8, and also includes any one or more of antigenic proteins SNX9, RND3, CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

[0080] Furthermore, the above-mentioned protein composition includes antigenic proteins FAM104B and MAGEA8, and also includes any one of antigenic proteins SNX9, RND3, CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

[0081] The present application provides an application of a protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises a protein composition, which includes antigenic proteins FAM104B and ACPP. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0082] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and ACPP, and also includes any one or more of the antigenic proteins SNX9, RND3, CCDC9, PDIK1L, YWHAZ, TTC1 and MAGEA8.

[0083] Furthermore, the above-mentioned protein composition includes the antigenic proteins FAM104B and ACPP, and also includes any one of the antigenic proteins SNX9, RND3, CCDC9, PDIK1L, YWHAZ, TTC1 and MAGEA8.

[0084] Furthermore, the above-mentioned antigen protein FAM104B includes a polypeptide having an amino acid sequence as shown in SEQ ID NO:1, or includes a polypeptide having at least 80% homology with the sequence SEQ ID NO:1 and having the same or substantially the same function, or a polypeptide having the same or substantially the same function formed by replacing, deleting or adding one or more amino acids in the amino acid sequence shown in SEQ ID NO:1, MGGCPVRKRRRNGSKEGNHHSTQPKRNKRNPIFQDSQDTEVFSWSDNESSSRINIPERASGPEGNLNQIVTEPDANFPQFLHEGLSKPVYVINWFMSFGPEIKLNTSQQGRNQAV (SEQ IDNO:1).

[0085] Furthermore, the above-mentioned antigen protein SNX9 includes a polypeptide having an amino acid sequence as shown in SEQ ID NO:2, or includes a polypeptide having at least 80% homology with the sequence SEQ ID NO:2 and having the same or substantially the same function, or a polypeptide having the same or substantially the same function formed by replacing, deleting or adding one or more amino acids in the amino acid sequence shown in SEQ ID NO:2 (SEQ ID NO:2).Further, the above-mentioned antigen protein RND3 is a polypeptide comprising an amino acid sequence as shown in SEQ ID NO:3, or a polypeptide having at least 80% homology with the sequence SEQ ID NO:3 and having the same or substantially the same function, or a polypeptide having the same or substantially the same function formed by replacing, deleting or adding one or more amino acids in the amino acid sequence shown in SEQ ID NO:3, MKERRASQKLSSKSIMDPNQNVKCKIVVVGDSQCGKTALLHVFAKDCFPENYVPTVFENYTASFEIDTQRIELSLWDTSGSPYYDNVRPLSYPDSDAVLICFDISRPETLDSVLKKWKGEIQEFCPNTKMLLVGCKSDLRTDVSTLVELSNHRQTPVSYDQGANMAKQIGAATYIECSALQSENSVRDIFHVATLACVNKTNKNVKRNKSQRATKRISHMPSRPELSAVATDLRKDKAKSCTVM (SEQID NO:3).

[0086] Furthermore, the above-mentioned antigen protein CCDC9 includes a polypeptide having an amino acid sequence as shown in SEQ ID NO:4, or includes a polypeptide having at least 80% homology with the sequence SEQ ID NO:4 and having the same or substantially the same function, or a polypeptide having the same or substantially the same function formed by replacing, deleting or adding one or more amino acids in the amino acid sequence shown in SEQ ID NO:4 (SEQ ID NO:4).

[0087] Furthermore, the antigen protein PDIK1L comprises a polypeptide having an amino acid sequence as shown in SEQ ID NO:5, or comprises a polypeptide having at least 80% homology with the sequence SEQ ID NO:5 and having the same or substantially the same function, or comprises a polypeptide having SEQ ID The amino acid sequence shown in NO:5 is substituted, deleted or added with one or more amino acids to form a polypeptide with the same or substantially the same function, MVSSQPKYDLIREVGRGSYGVVYEAVIRKTSARVAVKKIRCHAPENVELALREFWALSSIKSQHPNVIHLEECILQKDGMVQKMSHGSNSSLYLQLVETSLKGEIAFDPRSAYYLWFVMDFCDGGDMNEYLLSRKPNRKTNTSFMLQLSSALAFLHKNQIIHRDLKPDNILISQTRLDTSDLEPTLKVADFGLSKVCSASGQNPEEPVSVNKCFLSTACGTDFYMAPEVWEGHYTAKADIFALGIIIWAMLERITFIDTETKKELLGSYVKQGTEIVPVGEALLENPKMELLIPVKKKSMNGRMKQLIKEMLAANPQDRPDAFELELRLVQIAFKDSSWET (SEQID NO:5).

[0088] Further, the above-mentioned antigen protein YWHAZ is a polypeptide comprising an amino acid sequence as shown in SEQ ID NO:6, or a polypeptide having at least 80% homology with the sequence SEQ ID NO:6 and having the same or substantially the same function, or a polypeptide having the same or substantially the same function formed by substituting, deleting or adding one or more amino acids in the amino acid sequence shown in SEQ ID NO:6, MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN (SEQ ID NO:6).

[0089] Furthermore, the antigen protein TTC1 comprises a polypeptide having an amino acid sequence as shown in SEQ ID NO:7, or a polypeptide having at least 80% homology with the sequence SEQ ID NO:7 and having the same or substantially the same function, or a polypeptide having SEQ ID The amino acid sequence shown in NO:7 is replaced, deleted or added with one or more amino acids to form a polypeptide with the same or substantially the same function, MGEKSENCGVPEDLLNGLKVTDTQEAECAGPPVPDPKNQHSQSKLLRDDEAHLQEDQGEEECFHDCSASFEEEPGADKVENKSNEDVNSSELDEEYLIELKKNMSDEEKQKRREESTRLKEEGNEQFKKGDYIEAESSYSRALEMCPSCFQKERSILFSNRAAARMKQDKKEMAINDCSKAIQLNPSYIRAILRRAELYEKTDKLDEALEDYKSILEKDPSIHQAREACMRLPKQIEERNERLKEEMLGKLKDLGNLVLRPFGLSTENFQIKQDSSTGSYSINFVQNPNNNR (SEQ ID NO:7).

[0090] Furthermore, the antigen protein MAGEA8 comprises a polypeptide having an amino acid sequence as shown in SEQ ID NO: 8, or comprises a polypeptide having at least 80% homology with the sequence SEQ ID NO: 8 and having the same or substantially the same function, or comprises a polypeptide having SEQ ID The amino acid sequence shown in NO:8 is replaced, deleted or added with one or more amino acids to form a polypeptide with the same or substantially the same function, MLLGQKSQRYKAEEGLQAQGEAPGLMDVQIPTAEEQKAASSSSTLIMGTLEEVTDSGSPSPPQSPEGASSSLTVTDSTLWSQSDEGSSSNEEEGPSTSPDPAHLESLFREALDEKVAELVRFLLRKYQIKEPVTKAEMLESVIKNYKNHFPDIFSKASECMQVIFGIDVKEVDPAGHSYILVTCLGLSYDGLLGDDQSTPKTGLLIIVLGMILMEGSRAPEEAIWEALSVMGLYDGREHSVYWKLRKLLTQEWVQENYLEYRQAPGSDPVRYEFLWGPRALAETSYVKVLEHVVRVNARVRISYPSLHEEALGEEKGV (SEQ ID NO:8).

[0091] Furthermore, the antigen protein ACPP is a polypeptide comprising an amino acid sequence as shown in SEQ ID NO:9, or a polypeptide having at least 80% homology with the sequence SEQ ID NO:9 and having the same or substantially the same function, or a polypeptide having the same or substantially the same function formed by substituting, deleting or adding one or more amino acids in the amino acid sequence shown in SEQ ID NO:9, MRAAPLLLARAASLSLGFLFLLFFWLDRSVLAKELKFVTLVFRHGDRSPIDTFPTDPIKESSWPQGFGQLTQLGMEQHYELGEYIRKRYRKFLNESYKHEQVYIRSTDVDRTLMSAMTNLAALFPPEGVSIWNPILLWQPIPVHTVPLSEDQLLYLPFRNCPRFQELESE TLKSEEFQKRLHPYKDFIATLGKLSGLHGQDLFGIWSKVYDPLYCESVHNFTLPSWATEDTMTKLRELSELSLLSLYGIHKQKEKSRLQGGVLVNEILNHMKRATQIPSY KKLIMYSAHDTTVSGLQMALDVYNGLLPPYASCHLTELYFEKGEYFVEMHYRNETQHEPYPLMLPGCSPSCPLERFAELVGPVIPQDWSTECMTTNSHQGTEDSTD(SEQ ID NO:9).

[0092] Furthermore, the at least 80% homology mentioned above includes 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homology.

[0093] Furthermore, the above antigen protein is expressed in yeast cells and obtained through purification.

[0094] The present application also provides a method for preparing the above antigen protein, which specifically comprises the following steps:

[0095] (1) Using Gateway high-throughput cloning technology, the full-length cDNA of the antigen protein was cloned into the yeast expression vector pEGH-A to construct a yeast expression plasmid for the GST fusion protein;

[0096] (2) Transforming the yeast expression plasmid into Escherichia coli cells, amplifying and purifying the plasmid; performing restriction digestion and DNA sequencing verification on the purified plasmid, and selecting the correct plasmid to transform into yeast cells;

[0097] (3) Pick the transformed yeast clones, inoculate them into SC-Ura / Glucose liquid medium, and culture them with shaking at 30°C for 20 to 24 hours; transfer them to SC-Ura / Raffinose liquid medium, and culture them with shaking at 30°C overnight; when the OD600 absorbance value is greater than 1.0 on the second day, add galactose to a final concentration of 2%, and continue to culture them with shaking overnight; collect the yeast cells by centrifugation, and wash them twice with sterile water;

[0098] (4) Add lysis buffer and nickel beads, shake to break the cells, and recover the supernatant by centrifugation; add Glutathione Sepharose 4B beads to the supernatant, mix well, and shake at 4°C for 1 hour; collect the beads by centrifugation, and wash them three times with wash solution I and wash solution II respectively; add elution buffer, shake briefly to resuspend the beads, and shake at 4°C for 1 hour; centrifuge and collect the supernatant to obtain the antigen protein.

[0099] Furthermore, in the above-mentioned method for preparing the antigen protein, the components of the lysate include: 50mM Tris, pH 7.5, 100mM NaCl, 1mM EGTA, 10% Glycerol, 0.1% TritonX-100, 0.1% beta-mercaptoethanol (BME), 1mM PMSF (200mM in isopropanol), 50μM LLnL (50mM in DMSO), 1μM MG-132 (50mMin DMSO), Roche Protease inhibitor tablets (without EDTA) 1in 50ml.

[0100] Furthermore, in the above-mentioned method for preparing the antigen protein, the components of the washing solution I include: 50mM Tris, pH 7.5, 500mM NaCl, 1mM EGTA, 10% Glycerol, 0.1% TritonX-100, 0.1% beta-mercaptoethanol (BME), and 1mM PMSF.

[0101] Furthermore, in the above method for preparing the antigen protein, the components of the washing solution II include: 50 mM HEPES pH 7.5, 100 mM NaCl, 1 mM EGTA, 10% Glycerol, 0.1% beta-mercaptoethanol (BME), and 1 mM PMSF.

[0102] Furthermore, in the above-mentioned method for preparing the antigen protein, the eluent components include: 50 mM HEPES pH 8.0, 100 mM NaCl, 30% Glycerol, 40 mM Glutathione (Reduced form), and 0.03% TritonX-100.

[0103] The present application also provides a solid phase carrier, which is coated with any of the above-mentioned antigenic proteins or protein compositions.

[0104] The present application also provides the use of the above-mentioned antigen protein or protein composition in the preparation of a product for early diagnosis of lung cancer. The product comprises any of the above-mentioned antigen protein or protein composition. The antigen protein or protein composition can be used to detect lung cancer antibodies in serum, thereby being used for early diagnosis of lung cancer.

[0105] The present application also provides the use of the above-mentioned antigen protein or protein composition in the preparation of a kit for early diagnosis of lung cancer, wherein the kit comprises any of the above-mentioned antigen proteins or protein compositions, and the kit utilizes the antigen protein or protein composition to detect lung cancer autologous IgG antibodies in the serum of a subject, thereby being used for early diagnosis of lung cancer.

[0106] The present application also provides a kit for early diagnosis of lung cancer, which comprises any of the above-mentioned antigen proteins or protein compositions. The kit utilizes the antigen proteins or protein compositions to detect lung cancer autologous IgG antibodies in the serum of a subject, thereby being used for early diagnosis of lung cancer.

[0107] Furthermore, the signal detection methods used in the above-mentioned kit include visible light colorimetry, chemiluminescence, and fluorescence.

[0108] Furthermore, the above kit also includes a color developer, a serum dilution buffer, a washing solution and a stop solution.

[0109] The present application also provides the use of the above-mentioned kit for early diagnosis of lung cancer in the early diagnosis of lung cancer.

[0110] Furthermore, the above application includes the following steps:

[0111] S1: Obtain serum samples from subjects;

[0112] S2: Use the kit to detect the expression level of lung cancer auto-IgG antibodies in the serum samples of the subjects;

[0113] S3: Compare the expression level of lung cancer autologous IgG antibodies in the tested serum sample with a preset value. If the expression level is greater than the preset value, it is determined that the patient has lung cancer.

[0114] The present application also provides a device for early diagnosis of lung cancer, the device comprising:

[0115] A sample acquisition module, used to obtain a serum sample from a subject;

[0116] A sample detection module, including any of the above-mentioned kits for early diagnosis of lung cancer, used to detect the expression level of lung cancer autoimmune IgG antibodies in serum samples of subjects;

[0117] Data processing and result output module: compare the expression level of lung cancer autologous IgG antibodies in the serum samples of the subjects detected by the sample detection module with the preset value. If it is greater than the preset value, the result of lung cancer is output; otherwise, the result of not having lung cancer is output.

[0118] 3. Beneficial effects

[0119] Compared with the prior art, the present application has the following beneficial effects:

[0120] (1) The use of the antigen protein or protein composition provided in the present application in the early diagnosis of lung cancer, wherein the antigen proteins FAM104B, RND3, CCDC9, PDIK1L, and YWHAZ are newly screened antigen proteins in the present application, which can be used to detect lung cancer autologous IgG antibodies in serum, thereby being used for the early diagnosis of lung cancer, and the sensitivity, specificity, and the average value of sensitivity and specificity of a single antigen protein in the prior art are basically the same as, or even better.

[0121] (2) The application of the antigen protein or protein composition provided in the present application in the early diagnosis of lung cancer. The combination of the newly screened antigen protein of the present application or the combination of the antigen protein in the prior art can be used to detect lung cancer autologous IgG antibodies in serum, thereby being used for the early diagnosis of lung cancer. The average sensitivity and specificity are 54% to 88%. In particular, the protein composition containing the antigen proteins FAM104B and RND3 has an average sensitivity and specificity of more than 78%, which improves the accuracy of early diagnosis of lung cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0122] Figure 1 This is a representative scan image of the HuProt chip.

[0123] Figure 2 This is the reaction signal of the antigen protein CCDC9 on the chip. The left side is the lung cancer sample, and the right side is the healthy sample.

[0124] Figure 3 It is the OD value distribution of each antigen protein in 100 subject samples. DETAILED DESCRIPTION

[0125] The present application is further described below in conjunction with specific embodiments.

[0126] It should be noted that the terms such as "upper", "lower", "left", "right", "middle", etc. cited in this specification are only for the convenience of description and are not used to limit the scope of implementation. Changes or adjustments to their relative relationships should be regarded as the scope of implementation of this application without substantially changing the technical content.

[0127] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application belongs; the term "and / or" used herein includes any and all combinations of one or more of the associated listed items.

[0128] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. If the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0129] As used herein, the term "about" is used to provide flexibility and imprecision associated with a given term, measurement or value. The degree of flexibility for a particular variable can be easily determined by one skilled in the art.

[0130] As used herein, the term "at least one of" is intended to be synonymous with "one or more of." For example, "at least one of A, B, and C" explicitly includes only A, only B, only C, and also includes their respective combinations.

[0131] Concentration, amount and other numerical data can be presented in range format herein.It should be understood that such range format is only used for convenience and simplicity, and should be flexibly interpreted as not only including the numerical value clearly described as range limit, but also including all single numerical values ​​or sub-ranges contained in the range, just as each numerical value and sub-range are clearly described.For example, the numerical range of about 1 to about 4.5 should be interpreted as not only including the limit value of 1 to about 4.5 clearly described, but also including single numerals (such as 2,3,4) and sub-ranges (such as 1 to 3,2 to 4, etc.).The same principle is applicable to the scope of only narrating a numerical value, such as "less than about 4.5", which should be interpreted as including all the above-mentioned values ​​and ranges.In addition, no matter how the breadth of the described range or feature is, this explanation should be applicable.

[0132] Example 1

[0133] This embodiment provides screening of lung cancer-related antigens, which specifically includes the following steps:

[0134] 100 serum samples collected from 80 lung cancer patients and 20 healthy individuals were analyzed on the HuProt human proteome chip. The HuProt chip was provided by CDI Laboratories, Inc. Each HuProt v3.0 chip consists of 20,240 human full-length proteins, covering about 80% of the human proteome. There were no significant differences in age, gender, or smoking history between the lung cancer group and the healthy group.

[0135] The HuProt chip was first incubated in blocking buffer (PBS containing 0.1% (v / v) Tween 20 and 3% BSA) at room temperature for 1 hour, and then a 1:1,000 diluted serum sample was added and incubated at room temperature for 1 hour. Wash three times with 1×TBST with gentle shaking for 10 minutes each time. The chip was incubated with 3 ml of 1,000-fold diluted Alexa647-labeled goat anti-human IgG antibody (Jackson Immuno, USA) at room temperature in the dark for 1 hour. Subsequently, the HuProt chip was washed three times with 1×TBST and then rinsed three times with double distilled water. The HuProt chip was dried and scanned with a Genepix 4000B chip scanner (Molecular Devices, USA). The scanning results are shown as follows. Figure 1 As shown, the antibody signals on the chip were acquired using GenePix Pro 6.0 software.

[0136] To select candidate antigen proteins, the median of the foreground signal value (Fij) at a given protein point on the HuProt chip was extracted for analysis. Since each protein has two replicate points on the chip, the average value of Fij for each protein is taken as its signal intensity Fp. All Fp on 100 HuProt chips were quantile normalized, and then a t-test was performed to identify antigen proteins with significant differences between the lung cancer group and the healthy group. The selection criteria were that the p-value of the t-test was less than 0.05, and the average Fp of the lung cancer group was more than 1.5 times higher than that of the healthy group. Antigen proteins X1, X4, X8, X9, X14, X21, X25, X34, and X41 were identified by this method, and their IDs on the chip are shown in Table 1, of which some antigen proteins have been disclosed in prior applications (US20220003768A1). The reaction signal of the antigen protein CCDC9 (X9) on the chip is shown in Figure 2 As shown, the left side is lung cancer sample and the right side is healthy sample.

[0137] Table 1 Antigen protein ID on chip

[0138] Clone Id Antigenic protein Code JHU12283 FAM104B X1 JHU14342 SNX9 X4 JHU14238 RND3 X8 JHU08753 CCDC9 X9 JHU00348 PDIK1L X14 JHU00095 YWHA X21 JHU00476 TTC1 X25 JHU02742 MAGEA8 X34 JHU06144 ACPP X41

[0139] Example 2

[0140] This example provides a method for preparing the lung cancer-associated antigen protein in Example 1, which specifically comprises the following steps:

[0141] (1) Using Gateway high-throughput cloning technology, the full-length cDNA of the antigen protein was cloned into the yeast expression vector pEGH-A to construct a yeast expression plasmid for the GST fusion protein;

[0142] (2) Transforming the yeast expression plasmid into Escherichia coli cells, amplifying and purifying the plasmid; performing restriction digestion and DNA sequencing verification on the purified plasmid, and selecting the correct plasmid to transform into yeast cells;

[0143] (3) Pick the transformed yeast clones, inoculate them into 5 ml SC-Ura / Glucose liquid medium, and culture them with shaking at 30°C for 20 to 24 hours; transfer 1 ml into 300 ml SC-Ura / Raffinose liquid medium, and culture them with shaking at 30°C overnight; when the OD600 absorbance value is greater than 1.0 on the second day, add galactose to a final concentration of 2%, and continue to culture them with shaking overnight; collect the yeast cells by centrifugation, and wash them twice with sterile water;

[0144] (4) Add lysis buffer and nickel beads, shake to break the cells, and then centrifuge to recover the supernatant; add Glutathione Sepharose 4B beads to the supernatant, mix well, and shake at 4°C for 1 hour; collect beads by centrifugation, and wash them three times with wash buffer I and wash buffer II; add elution buffer, briefly shake to resuspend the beads, and shake at 4°C for 1 hour; centrifuge, take the supernatant, divide it into 10 μl, and freeze the rest in a -80°C refrigerator; the components of the lysis buffer include: 50mM Tris, pH 7.5, 100mM NaCl, 1mM EGTA, 10% Glycerol, 0.1% TritonX-100, 0.1% beta-mercaptoethanol (BME), 1mMPMSF (200mM in isopropanol), 50μM LLnL (50mM in DMSO), 1μM MG-132 (50mM in DMSO), Roche Protease inhibitor tablets (without EDTA) 1in 50ml; washing solution I components include: 50mM Tris, pH 7.5, 500mM NaCl, 1mM EGTA, 10% Glycerol, 0.1% TritonX-100, 0.1% beta-mercaptoethanol (BME), 1mM PMSF; washing solution II components include: 50mM HEPES pH 7.5, 100mM NaCl, 1mM EGTA, 10% Glycerol, 0.1% beta-mercaptoethanol (BME), 1mM PMSF; elution solution components include: 50mM HEPES pH 8.0, 100mM NaCl, 30% Glycerol, 40mM Glutathione (Reduced form), 0.03% TritonX-100.

[0145] (5) Perform SDA-PAGE gel electrophoresis and Coomassie Brilliant Blue staining on 10 μL of the protein to detect the molecular weight, concentration and purity of the target protein.

[0146] Example 3

[0147] This example provides the application of the lung cancer-associated antigens screened in Example 1 in the detection of lung cancer autoantibodies, including the following steps:

[0148] S1: Obtain serum samples from subjects, which were from the Affiliated Cancer Hospital of Sun Yat-sen University, including 20 healthy samples (HC1-HC20) and 80 lung cancer patients (LC1-LC80);

[0149] S2: Use the indirect ELISA method to detect autoantibodies, including using ELISA plates to coat 0.1 μg of lung cancer-related antigens, adding 100-fold diluted serum samples of subjects after blocking, using HRP-labeled anti-human IgG as the secondary antibody, terminating the reaction after washing and color development, and immediately detecting with an enzyme-labeled instrument. Specifically include:

[0150] (1) Dilute the antigen to 1 μg / mL using ELISA coating solution and add 100 μL of coating solution to the ELISA plate at 37°C for 1 h. The coating solution is 10 mM PBS (pH = 7.4);

[0151] (2) Cleaning: Fill the ELISA plate with Elisa cleaning solution, spin dry, and repeat 3 times. The cleaning solution includes: 10 mM PBS (PH = 7.4), 4% Tween-20;

[0152] (3) Blocking: Elisa blocking solution 200 μl / well, 4°C, overnight, wherein the blocking solution includes: 10 mM PBS (PH=7.4), 5% BSA, 4% Tween-20;

[0153] (4) Cleaning: Fill the ELISA plate with Elisa cleaning solution, spin dry, and repeat 5 times;

[0154] (5) Adding serum samples: two blank control wells were reserved for each plate as background, and the remaining 94 wells could detect 47 samples, with two replicate wells for each sample; 100 μL of 100-fold diluted serum sample was added to each well and incubated at 37° C. for 30 min, wherein the sample diluent included: 10 mM PBS (PH=7.4), 5% BSA;

[0155] (6) Cleaning: Fill the ELISA plate with Elisa cleaning solution, spin dry, and repeat 5 times;

[0156] (7) Secondary antibody: dilute HRP-labeled anti-human IgG secondary antibody with Elisa blocking solution; add 100 μL to each well and incubate at 37°C for 30 min;

[0157] (8) Cleaning: Fill the ELISA plate with Elisa cleaning solution, spin dry, and repeat 5 times;

[0158] (9) Color development: Mix color development solution A and color development solution B in a ratio of 1:1 and use it immediately after preparation; add 100 μL to each well and incubate at 37°C for 5 min;

[0159] (10) Termination: 50 μl / well of stop solution. Read the result immediately using an ELISA reader.

[0160] Result analysis:

[0161] The OD values ​​of 100 samples of subjects are as follows Figure 3 As shown, HC represents normal human samples and LC represents patient samples. Figure 3 It can be seen that there are differences in the expression levels of lung cancer autoantibodies in normal human samples and patient samples detected by 9 antigen proteins.

[0162] The maximum value or the second highest value in the normal sample is taken as the CUT-OFF value. When the detected OD value is greater than the CUT-OFF value, the subject is judged to have lung cancer. The above antigen proteins are combined, and the sensitivity and specificity of different combinations are shown in Table 2, wherein X1 is the antigen protein FAM104B, X4 is the antigen protein SNX9, X8 is the antigen protein RND3, X9 is the antigen protein CCDC9, X14 is the antigen protein PDIK1L, X21 is the antigen protein YWHAZ, X25 is the antigen protein TTC1, X34 is the antigen protein MAGEA8, and X41 is the antigen protein ACPP.

[0163] Table 2

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175] In the prior art, when two antigen proteins (CN117571985A) are selected, the average value is up to 79%, and the sensitivity is 58%. As shown in Table 2, when the number of antigen proteins is 2, the average value of the combination in the present application is 80%, and the sensitivity is 65%, which is an increase of 12.07%. It can be seen that the protein composition in the present application is conducive to improving the accuracy of early diagnosis of lung cancer.

Claims

1. Use of a protein composition in the preparation of a product for early diagnosis of lung cancer, characterized in that: The product comprises a protein composition, which includes antigenic proteins FAM104B and RND3. The diagnostic product utilizes the protein composition to detect lung cancer autologous IgG antibodies in serum, thereby being used for early diagnosis of lung cancer.

2. The use according to claim 1, characterized in that: The protein composition also includes any one or more of the antigenic proteins SNX9, CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

3. The use according to claim 2, characterized in that: The protein composition includes antigenic proteins FAM104B, SNX9 and RND3, and also includes any one or more of antigenic proteins CCDC9, PDIK1L, YWHAZ, TTC1, MAGEA8 and ACPP.

4. The use according to claim 2, characterized in that: The protein composition includes antigenic proteins FAM104B, RND3, MAGEA8, and any one or more of antigenic proteins SNX9, CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

5. The use according to claim 3 or 4, characterized in that: The protein composition includes antigenic proteins FAM104B, SNX9, RND3 and MAGEA8, and also includes any one or more of antigenic proteins CCDC9, PDIK1L, YWHAZ, TTC1 and ACPP.

6. The use according to claim 5, characterized in that: The protein composition includes antigenic proteins FAM104B, SNX9, RND3, TTC1 and MAGEA8, and also includes any one or more of antigenic proteins CCDC9, PDIK1L, YWHAZ and ACPP.

7. The use according to claim 6, characterized in that: The protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, TTC1 and MAGEA8, and also includes any one or more of antigenic proteins PDIK1L, YWHAZ and ACPP.

8. The use according to claim 7, characterized in that: The protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, PDIK1L, TTC1 and MAGEA8, and also includes antigenic proteins YWHAZ and / or ACPP.

9. The use according to claim 8, characterized in that: The protein composition includes antigenic proteins FAM104B, SNX9, RND3, CCDC9, PDIK1L, TTC1 and MAGEA8, and also includes antigenic proteins YWHAZ and ACPP.

10. The use according to claim 2, characterized in that: The antigen protein FAM104B is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 1; The antigen protein SNX9 is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 2; The antigen protein RND3 is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 3; The antigen protein CCDC9 is a polypeptide having an amino acid sequence as shown in SEQ ID NO:4; The antigen protein PDIK1L is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 5; The antigen protein YWHAZ is a polypeptide having an amino acid sequence as shown in SEQ ID NO: 6; The antigen protein TTC1 is a polypeptide having an amino acid sequence as shown in SEQ ID NO:7; Antigenic protein X24 is a polypeptide having an amino acid sequence as shown in SEQ ID NO:8; The antigen protein ACPP is a polypeptide with the amino acid sequence shown in SEQ ID NO:

9.

11. Use of a protein composition in the preparation of a kit for early diagnosis of lung cancer, characterized in that: The kit comprises the protein composition according to any one of claims 1 to 10, and the kit uses the protein composition to detect lung cancer autologous IgG antibodies in the serum of a subject, thereby being used for early diagnosis of lung cancer.

12. The use of the kit for early diagnosis of lung cancer as claimed in claim 11, characterized in that: The steps include: S1: Obtain serum samples from subjects; S2: Use the kit to detect the expression level of lung cancer auto-IgG antibodies in the serum samples of the subjects; S3: Compare the expression level of lung cancer autologous IgG antibodies in the tested serum sample with a preset value. If the expression level is greater than the preset value, it is determined that the patient has lung cancer.

13. A device for early diagnosis of lung cancer, characterized in that: The device comprises: A sample acquisition module, used to obtain a serum sample from a subject; A sample detection module, comprising the kit for early diagnosis of lung cancer as described in claim 11, used for detecting the expression level of lung cancer autologous IgG antibodies in a serum sample of a subject; Data processing and result output module: compare the expression level of lung cancer autologous IgG antibodies in the serum samples of the subjects detected by the sample detection module with the preset value. If it is greater than the preset value, the result of lung cancer is output; otherwise, the result of not having lung cancer is output.

Images