Biomarker CERS1 gene for prognosis diagnosis of colorectal cancer and application of biomarker CERS1 gene

Abstract

The invention provides a biomarker CERS1 gene for prognostic diagnosis of colorectal cancer and application thereof, and belongs to the technical field of prognostic diagnosis of colorectal cancer. In combination with clinical database information of colorectal cancer, CERS1 expression conditions are explored on the aspects of molecular level, animal models, clinical tissue samples and the like; and low expression of CERS1 in colon cancer tissues is found and confirmed. The relation between the CERS1 expression and the survival condition of a clinical case is analyzed, and it is proved that the low CERS1 expression is related to the poor overall survival rate and the disease-free survival rate. Therefore, the CERS1 can be used as a specific marker gene for prognosis of the colon cancer, and prognosis judgment of the colon cancer can be realized, so that the death rate of the colon cancer is reduced; compared with the traditional detection means, the method is faster, more specific, more sensitive and more accurate.

Description

Technical Field

[0001] The present invention belongs to the technical field of colorectal cancer prognosis diagnosis, and in particular relates to a biomarker CERS1 gene for colorectal cancer prognosis diagnosis and its application. Background Art

[0002] Colorectal cancer, a common malignancy worldwide, faces a severe and growing incidence and mortality rate, posing a serious threat to the lives and health of the general public. Clinical practice has demonstrated that early diagnosis and treatment are key to reducing colorectal cancer mortality. Therefore, fully understanding the molecular mechanisms underlying the development and progression of colorectal cancer is crucial for achieving early, accurate diagnosis and effective treatment, and is crucial for improving patient prognosis and enhancing quality of life.

[0003] Currently, clinical prognostic assessment for colorectal cancer relies primarily on traditional testing methods, such as the TNM staging system. While these traditional methods have played an important role in the diagnosis and treatment of colorectal cancer, they have significant limitations. The TNM staging system, based primarily on clinicopathological indicators such as tumor size, lymph node metastasis, and distant metastasis, fails to adequately account for individual patient differences and tumor heterogeneity. This results in limited accuracy and personalization in prognostic assessment, making it difficult to meet the demands of clinical precision diagnosis and treatment.

[0004] With the continuous deepening of research in the field of life sciences and the continuous accumulation of evidence-based medicine, molecular markers have gradually become a research hotspot in the field of tumor diagnosis and treatment due to their unique advantage of revealing the essence of disease occurrence and development at the molecular level. The precision diagnosis and treatment model based on the molecular level is also profoundly changing the current clinical practice of colorectal cancer. However, although molecular markers have shown great potential in the diagnosis and treatment of colorectal cancer, there is still a lack of specific molecular targets and related products on the market that can accurately predict the risk of colorectal cancer metastasis and conduct effective prognosis assessment. Therefore, the development of precision diagnosis and prognosis assessment products based on new molecular targets has very important clinical significance and broad application prospects for improving the diagnosis and treatment of colorectal cancer and improving patient prognosis. Summary of the Invention

[0005] In view of this, the object of the present invention is to provide a biomarker CERS1 gene for the prognosis and diagnosis of colorectal cancer and its application.

[0006] The present invention provides a biomarker for the prognosis and diagnosis of colorectal cancer, wherein the biomarker is the CERS1 gene.

[0007] Preferably, when the expression level of the CERS1 gene is significantly low, the patient has a poor prognosis and a significantly shortened five-year survival period.

[0008] The present invention provides the use of a reagent for detecting the biomarker in preparing a colorectal cancer prognosis diagnosis kit.

[0009] Preferably, the reagent comprises an anti-CERS1 antibody.

[0010] The present invention provides use of a reagent for overexpressing the CERS1 gene in preparing a drug for treating colorectal cancer.

[0011] Preferably, the reagent for overexpressing the CERS1 gene includes a recombinant vector overexpressing the CERS1 gene, a cell overexpressing the CERS1 gene, or a small molecule compound that promotes the expression of the CERS1 gene.

[0012] Preferably, overexpression of the CERS1 gene inhibits colorectal cancer tumorigenesis.

[0013] Compared with existing technologies, the present invention has the following beneficial effects: The present invention provides a biomarker, the CERS1 gene, for the prognosis and diagnosis of colorectal cancer. Combining information from a colorectal cancer clinical database, the present invention explored CERS1 expression at the molecular level, in animal models, and in clinical tissue samples, discovering and confirming that CERS1 is lowly expressed in colon cancer tissue. By analyzing the relationship between the survival status of clinical cases and CERS1 expression, it was demonstrated that low CERS1 expression is associated with poor overall survival and disease-free survival. This confirms that CERS1 can serve as a specific marker gene for the prognosis of colon cancer, enabling prognostic judgment of colon cancer and thus reducing its mortality rate. Compared with traditional detection methods, the present invention is faster, more specific, more sensitive, and more accurate.

[0014] Furthermore, the present invention also conducted in vivo experiments to detect the effect of overexpression of the CERS1 gene on the tumorigenicity of colorectal cancer. Compared with the control group (Vector), the mice in the experimental group (OE-CERS1) inoculated with cells overexpressing CERS1 formed smaller tumors, lighter tumor weights, and a slower tumor growth curve, indicating that CERS1 inhibits the tumorigenicity of colorectal cancer.

[0015] The present invention also conducted in vivo experiments to verify the therapeutic effect of overexpressing the CERS1 gene on colorectal cancer. Compared with the control group (Vector), the number of Ki-67 positive cells in the OE-CERS1 group was smaller, further confirming that overexpressing the CERS1 gene can inhibit the tumorigenicity of colorectal cancer in vivo. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 Analyze the expression of CERS1 in colorectal cancer patient tissues for the TCGA database;

[0017] Figure 2Immunohistochemical staining was used to detect the expression of CERS1 in adjacent tissues and colorectal cancer tissues.

[0018] Figure 3 Detect the expression of CERS1 in colorectal cancer tissues for IHC grading assessment;

[0019] Figure 4 Detect the expression of CERS1 in colorectal cancer tissues for IHC grading assessment;

[0020] Figure 5 Comparison of tumor sizes between the experimental group (OE-CERS1) and the control group (Vector) inoculated with CERS1-overexpressing cells. The left figure is a photograph, and the right figure is a curve of tumor volume changes.

[0021] Figure 6 Comparison of tumor weights between the experimental group inoculated with CERS1-overexpressing cells (OE-CERS1) and the control group (Vector);

[0022] Figure 7 The figure shows the results of Ki-67 immunohistochemical staining of tumors formed in the experimental group (OE-CERS1) and the control group (Vector) inoculated with cells overexpressing CERS1.

[0023] Figure 8 Kaplan-Meier analysis was performed to determine the relationship between CERS1 expression level and overall survival in patients with colorectal cancer. DETAILED DESCRIPTION

[0024] The present invention provides a biomarker for the prognosis and diagnosis of colorectal cancer, wherein the biomarker is the CERS1 gene. In the present invention, when the expression level of the CERS1 gene is significantly low, the patient has a poor prognosis and a significantly shortened five-year survival period.

[0025] The present invention also provides the use of a reagent for detecting the biomarker in preparing a colorectal cancer prognosis diagnosis kit.

[0026] The present invention has no particular limitation on the type of the reagent, and any reagent conventionally used in the art for detecting the expression level of the CERS1 gene can be used. In a specific implementation, the reagent includes an anti-CERS1 antibody.

[0027] The present invention also provides use of a reagent for overexpressing the CERS1 gene in preparing a drug for treating colorectal cancer.

[0028] In the present invention, the reagent for overexpressing the CERS1 gene preferably includes a recombinant vector overexpressing the CERS1 gene, a cell overexpressing the CERS1 gene, or a small molecule compound that promotes the expression of the CERS1 gene, such as a transcription activator, a signal pathway activator, and the like.

[0029] In the present invention, overexpression of the CERS1 gene inhibits colorectal cancer tumorigenesis, which is specifically manifested in that after overexpression of the CERS1 gene, the formed tumors are smaller, lighter in weight, and have a slower tumor growth curve.

[0030] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0031] 1) The colorectal cancer tissue chip used in the present invention was purchased from Shanghai Shengyang Biotechnology Co., Ltd. with the catalog number 2201.

[0032] 2) Hematoxylin stain was purchased from Wuhan Sewell Biotechnology Co., Ltd., product number G1004-100ML.

[0033] 3) 1× phosphate buffered saline (1× PBS buffer) was purchased from VICMED, China, with the catalog number VC2001P.

[0034] 4) Rabbit two-step detection kit was purchased from Beijing Zhongshan Jinqiao Biotechnology Co., Ltd., catalog number PV9001.

[0035] 5) Tissue microarrays of 80 colorectal cancer patients' paracancerous and cancerous tissues containing clinical prognostic case information were purchased from Hunan Aifang Biotechnology Co., Ltd.; 40 cancerous and paracancerous tissues were obtained from patients diagnosed with colorectal cancer during colonoscopy at the Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University.

[0036] 6) Anti-CERS1 antibody (Anti-CERS1 antibody HPA045724-E) was purchased from Wuhan Aimi Technology Co., Ltd.

[0037] 7) DAB color development kit (20×) was purchased from Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. with the catalog number ZLI-9018.

[0038] 8) Anhydrous ethanol was purchased from Shanghai Hushi Chemical Co., Ltd.

[0039] 9) Isopropyl alcohol was purchased from Shanghai Hushi Chemical Co., Ltd.

[0040] 10) The cells used in the present invention are human colorectal cancer cell line HCT116 and human embryonic kidney epithelial cell line HEK293T, both purchased from ATCC, USA.

[0041] 11) DMEM high glucose medium (containing double antibodies) was purchased from Jiangsu KeyGen Biotech Co., Ltd. with the catalog number KGL-1206-500.

[0042] 12) Human myc-CERS1 overexpression plasmid (lentivirus) was provided by Wuhan Hewu Biotechnology Co., Ltd.

[0043] 13) Polyethylenimine (PEI) was purchased from Sigma, USA.

[0044] 14) Matrigel was purchased from Corning, USA.

[0045] 15) BALB / C-Nude mice were purchased from Guizhou Bio-Han Biotechnology Co., Ltd.

[0046] Example 1

[0047] Analysis of CERS1 expression in colorectal cancer tissues using the TCGA database

[0048] 1. Experimental Procedure

[0049] from TCGA database We downloaded the STAR-counts data and corresponding clinical information for colorectal cancer from (https: / / portal.gdc.cancer.gov). We then extracted the data in TPM format and performed log2(TPM+1) normalization. Finally, we retained samples with both RNAseq data and clinical information, resulting in a total of 327 samples for subsequent analysis.

[0050] We used the log-rank test to compare the survival differences between the two groups in the KM survival analysis. For Kaplan-Meier curves, we derived p-values ​​and hazard ratios (HRs) with 95% confidence intervals (CIs) using the log-rank test and univariate Cox regression.

[0051] We used R software version 4.0.3 for statistical analysis. Results were considered statistically significant when the P value was less than 0.05.

[0052] 2. Experimental Results

[0053] The results of TCGA database analysis are as follows Figure 1 As shown in the results, the expression level of CERS1 in 286 primary tumor tissues was significantly lower than that in 41 normal tissues, indicating that CERS1 is underexpressed in colon cancer tissues.

[0054] Example 2

[0055] Immunohistochemical staining to detect the expression of CERS1 in adjacent tissues and colorectal cancer tissues

[0056] 1. Experimental Procedure

[0057] To further explore the expression of CERS1 at the protein level, the inventors used immunohistochemistry staining to detect the expression of CERS1 in tumor and adjacent tissue samples from 40 colorectal cancer patients and in tumor and adjacent tissue chips from 80 colorectal cancer patients containing prognostic pathological information.

[0058] Baking: Place the slides containing the tissue in a 60°C oven overnight. Dewaxing and hydration: Place the sections in xylene (I) and (II) for 30 minutes each, then place them in anhydrous ethanol (I), (II), 95% ethanol, 90% ethanol, 85% ethanol, 80% ethanol, 70% ethanol, and distilled water for 5 minutes each. Removal of endogenous peroxidase: Cover the tissue with 3% H2O2, place in a humidified chamber, and incubate at room temperature in the dark for 10 minutes. Wash with 1× PBS three times, 5 minutes each time.

[0059] Antigen retrieval: Using high temperature and high pressure retrieval - Pour enough citric acid (pH 6.0) retrieval solution into the pressure cooker to ensure that the slices are covered. After the liquid boils, add the slices and cover the lid. After the pressure cooker starts to vent, count down for 3 minutes and perform antigen retrieval. After retrieval is complete and the pressure drops to normal pressure, open the lid and let the slices warm at room temperature. Then wash them three times with 1× PBS for 5 minutes each.

[0060] Blocking: Cover the sections with 1% goat serum blocking solution and incubate in a humidified box at room temperature for 30 minutes in the dark.

[0061] Overnight primary antibody: CERS1 was diluted 1:250 with PBS, and each section was covered with approximately 50 μL. The sections were placed in a humidified chamber at 4°C overnight. The next day, the sections were allowed to warm up at room temperature for 30 minutes, and then washed three times with 1× PBS for 5 minutes each time to remove excess primary antibody.

[0062] Incubation with secondary antibody: Select the corresponding secondary antibody according to the primary antibody. Refer to the secondary antibody instructions for use - incubate the sections with enhancement solution, incubate in a wet box at room temperature for 20 minutes, wash three times with 1× PBS, each time for 5 minutes, incubate with antibody solution, incubate in a wet box at room temperature for 20 minutes, and wash three times with 1× PBS, each time for 5 minutes;

[0063] DAB color development: Prepare DNA color development solution, add 1 drop of solution B to 1 mL of solution A, mix well, protect from light, prepare immediately before use, add the color development solution to the slices, incubate in the dark for several minutes depending on the condition of the slices, until a brown precipitate appears on the slices, rinse the slices with distilled water to terminate the color development reaction;

[0064] Hematoxylin counterstaining: After the tissue sections have developed color, rinse them thoroughly with distilled water and then immerse them in hematoxylin for 3 to 5 minutes for counterstaining; hydrochloric acid acidification and lithium carbonate anti-blueing: acidify with 1% hydrochloric acid, draw the solution several times, rinse the remaining liquid with distilled water, and place it in saturated lithium carbonate for 1 to 2 minutes for anti-blueing.

[0065] Dehydration and mounting: Dehydrate in the reverse order of dewaxing, mount with gum, observe under an optical microscope, and take photos for analysis.

[0066] 2. Experimental Results

[0067] The results of immunohistochemical staining for the expression of CERS1 in paracancerous tissues and colorectal cancer chip samples are as follows: Figure 2 As shown, CERS1 is lowly expressed in colorectal cancer tissues.

[0068] Example 3

[0069] Verification of CERS1 expression in colorectal cancer tissues by IHC grading

[0070] 1. Experimental Procedure

[0071] Immunohistochemical (IHC) staining was graded by three professionals in a double-blind manner: a brownish-yellow granular precipitate in the cytoplasm or cell membrane was considered positive. The percentage of positive cells was first graded, with scores ranging from 0 to 4, including none, 1-25%, 26-50%, 51-75%, and 76-100%, respectively. Staining intensity was then graded from 0 to 3, with no staining (negative) receiving 0, yellow (weakly positive) receiving 1, brownish-yellow (positive) receiving 2, and yellowish-brown (strongly positive) receiving 3. The product of these two scores was combined to create a total score of 12, with the highest score representing a stronger positive result.

[0072] 2. Experimental Results

[0073] The experimental results are as follows Figure 3-4 As shown in Figure 3, the expression of CERS1 in tumor tissues of colorectal cancer patients was significantly lower than that in adjacent adjacent tissues.

[0074] Example 4

[0075] In vivo experiments to detect the effect of overexpression of CERS1 on the tumorigenicity of colorectal cancer

[0076] 1. Experimental Procedure

[0077] Virus preparation: 293T cells were seeded in a 60 mm dish in advance. The next day, when the cells reached 80-90% confluency, transfection was performed using polyethylenimine (PEI). A total plasmid (μg):PEI (μL) ratio of 8:3 was used for transfection. The core plasmid (CERS1) and packaging plasmid were combined at a ratio of 4:3:1, for a total of 8 μg of plasmid. 500 μL of serum-free medium was added to a 1.5 mL EP tube. The total plasmid and PEI were then added to the tube sequentially, pipetting to mix thoroughly. The tube was then incubated at room temperature for 15 minutes. The medium in the 60 mm dish was removed, and the dish was washed twice with 1x PBS. 4.5 mL of serum-free medium was then added. After 15 minutes, the mixture from the EP tube was suspended and added to the dish. After cross-mixing, the cells were incubated in an incubator for further culture. 6-8 hours after transfection, the medium was replaced with 10% serum-containing medium and culture continued. 48 h after transfection, the virus solution was collected.

[0078] Viral infection: HCT116 cells were seeded in a 60mm culture dish and infected the next day when the cell confluence reached 30-40%. The culture medium in the culture dish was discarded and washed twice with 1×PBS. 2mL of virus solution + 2μL Polybrene reagent was added to a 15mL centrifuge tube, pipetted to mix well, and then added to a 60mm culture dish. After shaking, the dish was placed in an incubator for culture. After 6-8 hours, fresh complete culture medium was replaced and cultured at 37°C and 5% CO2. After 48 hours, puromycin was added to the culture dish at a final concentration of 1.0μg / mL to select the cells. The selection was continued for 72 hours. After the cells were fully grown, they were digested and subcultured for expansion.

[0079] Subcutaneous tumor inoculation: The expanded cultured HCT116 cells that stably overexpress CERS1 were digested and counted, and the cells were resuspended in sterile 1× PBS to adjust the cell density to 1×10 8 100 μL / mL. Mix an equal volume of cell suspension and Matrigel thoroughly into a 2 mL EP tube. Inoculate each BALB / C-nude male mouse with 200 μL of this mixture. Observe the mice regularly, monitor tumor volume, and record it. Terminate the experiment when a significant difference in tumor size between the CERS1 overexpression group and the empty vector group becomes apparent. Sacrifice the mice by cervical dislocation, and collect the tumors.

[0080] 2. Experimental Results

[0081] The experimental results are as follows Figure 5 and Figure 6As shown, compared with the control group (Vector), the experimental group (OE-CERS1) inoculated with CERS1-overexpressing cells developed smaller tumors, lighter tumor weights, and slower tumor growth curves in the OE-CERS1 group, indicating that CERS1 inhibits the tumorigenicity of colorectal cancer.

[0082] Example 5

[0083] In vivo experiments verify the therapeutic effect of overexpression of CERS1 gene on colorectal cancer (Ki-67 staining method)

[0084] 1. Experimental Procedure

[0085] Ten 6- to 8-week-old BALB / C-Nude male mice were randomly divided into two groups according to their body weight: control group (Vector) and CERS1 overexpression group (OE-CERS1). Cells in each group were expressed at 1×10 8 Resuspend in sterile 1×PBS at a density of cells / mL, take an equal volume of cell suspension and Matrigel matrix gel and mix thoroughly into a 2mL EP tube, and inoculate 200μL of the mixture of cell suspension and matrix gel into each BALB / C-Nude male mouse. Observe the mice regularly, monitor the tumor volume and record it. When the difference in tumor size between the CERS1 overexpression group and the empty vector group is more obvious, terminate the experiment. Sacrifice the mice by cervical dislocation and collect the tumors. Fix in 4% paraformaldehyde for three days, transfer to 75% ethanol, and store at room temperature;

[0086] Dehydration: Tumor tissue was placed in 75% ethanol for 1 hour, 85% ethanol for 1 hour, and 95% ethanol at room temperature overnight.

[0087] Transparency: On the second day, replace with fresh 95% ethanol for 1 hour, 100% ethanol twice for 30 minutes each, and xylene twice for 30 minutes each, to make the tissue transparent and amber in color;

[0088] Wax dipping: Preheat the wax in a 70℃ oven and soak the above transparent tissue in it for 3-4 hours;

[0089] Wax block: Pour the melted embedding wax into the embedding mold, quickly put the wax-soaked tissue block in, insert the prepared label, wait for the wax to solidify, and store at -20℃ for later use;

[0090] Sectioning: Section the paraffin tissue at a thickness of 4 μm. Place the sectioned paraffin tissue in a 37°C water bath, fully unfold the sections, and attach the sections to a poly-lysine-coated slide.

[0091] Baking: Place the slides containing tissue in a 60°C oven overnight;

[0092] Dewaxing and hydration: Place the sections in xylene (I) and (II) for 30 min each, then place them in anhydrous ethanol (I), (II), 95% ethanol, 90% ethanol, 85% ethanol, 80% ethanol, 70% ethanol, and distilled water for 5 min each;

[0093] To remove endogenous peroxidase, add 3% H2O2 to the tissue, place in a humidified chamber, and incubate at room temperature in the dark for 10 minutes; then wash with 1× PBS three times, 5 minutes each time;

[0094] Antigen retrieval: High-temperature, high-pressure retrieval: Pour enough citric acid (pH 6.0) retrieval solution into a pressure cooker to cover the sections. Bring the solution to a boil, then add the sections. Cover the pressure cooker and wait for the pressure cooker to begin venting for 3 minutes before performing antigen retrieval. After retrieval is complete and the pressure has returned to normal, open the lid, warm the sections to room temperature, and then wash them three times with 1× PBS for 5 minutes each.

[0095] Blocking: Cover the sections with 1% goat serum blocking solution and incubate in a humidified box at room temperature for 30 minutes in the dark.

[0096] Overnight primary antibody: Dilute Ki-67 and CERS1 with PBS at a ratio of 1:250, cover each section with approximately 50 μL, and place in a humidified chamber at 4°C overnight. The next day, warm the chamber to room temperature for 30 minutes, then wash three times with 1× PBS for 5 minutes each time to remove excess primary antibody.

[0097] Incubation with secondary antibody: Select the corresponding secondary antibody according to the primary antibody. Refer to the secondary antibody instructions for use - incubate the sections with enhancement solution, incubate in a wet box at room temperature for 20 minutes, wash three times with 1× PBS, 5 minutes each time, incubate with antibody solution, incubate in a wet box at room temperature for 20 minutes, and wash three times with 1× PBS, 5 minutes each time;

[0098] DAB color development: Prepare DNA color development solution, add 1 drop of solution B to 1 mL of solution A, mix well, protect from light, prepare immediately before use, add the color development solution to the slices, incubate in the dark for several minutes depending on the condition of the slices, until a brown precipitate appears on the slices, rinse the slices with distilled water to terminate the color development reaction;

[0099] Hematoxylin counterstaining: After the tissue sections have developed color, rinse them thoroughly with distilled water and then soak them in hematoxylin for counterstaining for 3 to 5 minutes.

[0100] Acidification with hydrochloric acid and blueing with lithium carbonate: acidify with 1% hydrochloric acid, draw out several times, rinse the remaining liquid with distilled water, and place in saturated lithium carbonate for 1-2 minutes to blue.

[0101] Dehydration and mounting: Dehydrate in the reverse order of dewaxing, mount with gum, observe under an optical microscope, and take photos for analysis.

[0102] 2. Experimental Results

[0103] Immunohistochemical staining results of the tumor Figure 7 As shown, compared with the Vector group, the number of Ki-67 positive cells in the OE-CERS1 group was less, further verifying the ability of CERS1 to inhibit the tumorigenesis of colorectal cancer in vivo.

[0104] Example 6

[0105] Kaplan-Meier analysis of five-year survival in patients with CERS1 expression

[0106] 1. Experimental Procedure

[0107] 59 colorectal cancer patients with prognostic clinicopathological information were divided into two groups according to IHC score CERS1 Low 、CERS1 High (CERS1: 0-4 is considered low expression, and 6-12 is considered high expression.) Kaplan-Meier analysis was used to analyze the five-year survival of the two groups of patients, and survival curves were drawn.

[0108] 2. Experimental Results

[0109] Kaplan-Meier analysis of the relationship between CERS1 expression and overall survival in patients with colorectal cancer. Figure 8 As shown, the five-year overall survival rate of colorectal cancer patients with high CERS1 expression (CERS1 High) was significantly higher than that of colorectal cancer patients with low CERS1 expression (CERS1 Low). These clinical data suggest that low CERS1 expression leads to poor prognosis in colorectal cancer patients.

[0110] Example 7

[0111] Fisher test was used to investigate the correlation between CERS1 expression and clinicopathological characteristics of patients with colorectal cancer

[0112] 1. Experimental Procedure

[0113] Fisher's test was used to further explore the correlation between CERS1 expression and clinicopathological characteristics of colorectal cancer patients and clarify its clinical significance in colorectal cancer.

[0114] 2. Experimental Results

[0115] The results are shown in Table 1. In colorectal cancer tissues, low expression of CERS1 accounted for 76.3% (45 / 59) and high expression accounted for 23.7% (14 / 59). Low expression of CERS1 was significantly positively correlated with tumor size, lymph node metastasis and distant metastasis.

[0116] From the above examples, it can be seen that low expression of CERS1 is associated with poor overall survival rate. Therefore, it is determined that CERS1 can be used as a specific marker gene for the prognosis of colon cancer, which can realize the prognosis judgment of colon cancer and thus reduce the mortality rate of colon cancer.

[0117] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A biomarker for the prognosis of colorectal cancer, characterized in that: The biomarker is the CERS1 gene.

2. The biomarker according to claim 1, characterized in that When the expression level of the CERS1 gene is significantly low, the patient's prognosis is poor and the five-year survival period is significantly shortened.

3. Use of a reagent for detecting the biomarker according to claim 1 in the preparation of a colorectal cancer prognosis diagnostic kit.

4. The use according to claim 3, characterized in that The reagents include anti-CERS1 antibodies.

5. Use of reagents that overexpress the CERS1 gene in the preparation of drugs for the treatment of colorectal cancer.

6. The use according to claim 5, characterized in that The reagent for overexpressing the CERS1 gene includes a recombinant vector for overexpressing the CERS1 gene, a cell for overexpressing the CERS1 gene, or a small molecule compound that promotes the expression of the CERS1 gene.

7. The use according to claim 5, characterized in that Overexpression of the CERS1 gene inhibits colorectal cancer tumorigenesis.

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