DNAJC9 and its applications

By using DNAJC9 as a tumor-specific expression protein, immunohistochemistry and immunofluorescent markers for B-cell lymphoma diagnosis are prepared, which solves the complex and costly diagnosis of B-cell lymphoma in the prior art, and achieves a more efficient and accurate diagnosis.

CN115201477BActive Publication Date: 2025-04-25SHANGHAI NINTH PEOPLES HOSPITAL SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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Patent Information

Application Number
CN202210814396.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-07-12
Publication Date
2025-04-25
Estimated Expiration
2042-07-12

AI Technical Summary

Technical Problem

The existing pathological diagnosis methods of B cell lymphoma are complex and costly, and the traditional B lymphocyte markers are not tumor-specific, which leads to difficulty in differential diagnosis.

Method used

DNAJC9 is used as a tumor-specific expression protein to prepare immunohistochemistry and immunofluorescence markers for the diagnosis of B-cell lymphoma, and is used to prepare diagnostic kits.

Benefits of technology

Through the application of DNAJC9, the cost of diagnosis of B-cell lymphoma is reduced, the problem of differential diagnosis of lymphocyte infiltration caused by reactive lymphoid tissue hyperplasia or inflammation is solved, and the accuracy and efficiency of diagnosis are improved.

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Abstract

The present invention relates to DNAJC9 and applications thereof, and belongs to the technical field of biomedicine. The present invention provides applications of DNAJC9 in preparing a diagnostic kit for B-cell lymphoma; and applications of DNAJC9 in preparing a differential diagnostic kit for lymphocyte infiltration caused by reactive lymphoid tissue hyperplasia or inflammation.
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Description

Technical Field

[0001] The present invention relates to DNAJC9 and application thereof, and belongs to the technical field of biomedicine. Background Art

[0002] At present, the pathological diagnosis criteria for B-cell lymphoma are mainly based on the classification of hematopoietic and lymphoid tissue tumors formulated by the World Health Organization (WHO). The diagnosis of these diseases is based on a comprehensive evaluation of parameters such as cell morphology, immunophenotype, genetics, and clinical manifestations. At present, classical histopathological examination is still the main method for diagnosing lymphoma, while immunohistochemical staining is an important means for diagnosing lymphoma and judging tumor subtypes. Cytogenetics and molecular biology and other detection technologies are important supplements for lymphoma diagnosis. Usually, positive results of immunohistochemical staining of B lymphocyte markers such as CD20, CD79a, PAX5 combined with histopathological characteristics can confirm B-cell lymphoma. However, the main defects of the prior art are: the existing pathological diagnosis of B-cell lymphoma requires a comprehensive diagnosis in combination with histopathology, immunohistochemical staining and molecular biology, with high diagnostic costs, complex methods, and long diagnostic cycles. In terms of immunohistochemical staining, the staining results of B lymphocyte markers are often used in the diagnosis of B-cell lymphoma. However, B lymphocyte markers are not tumor-specific immunohistochemical markers and are also positive in lymphocyte infiltration caused by reactive lymphoid tissue hyperplasia or inflammation, making differential diagnosis difficult. Therefore, the technical field urgently needs to obtain a tumor-specific B cell lymphoma molecular immunohistochemical marker for B cell lymphoma diagnosis. Summary of the invention

[0003] The purpose of the present invention is to solve the technical problem of how to obtain B cell lymphoma immunohistochemistry and immunofluorescence markers based on tumor-specific expression proteins and use them for B cell lymphoma diagnosis.

[0004] In order to achieve the purpose of solving the above problems, the technical solution adopted by the present invention is to provide the use of DnaJ heat shock protein family member C9 (DNAJC9) in the preparation of a B cell lymphoma diagnostic kit.

[0005] The present invention provides application of DNAJC9 in preparing a differential diagnosis kit for lymphocyte infiltration caused by reactive lymphoid tissue hyperplasia or inflammation.

[0006] Compared with the prior art, the present invention has the following beneficial effects:

[0007] The present invention obtains a protein DNAJC9 specifically expressed in tumor tissue of B-cell lymphoma, and reduces the cost of pathological diagnosis by preparing a diagnostic kit of immunohistochemistry and immunofluorescence markers for pathological diagnosis of B-cell lymphoma; and solves the problem encountered in the differential diagnosis of lymphocyte infiltration caused by reactive lymphoid tissue hyperplasia or inflammation in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 This is a process diagram of the present invention for screening diagnostic markers that are specifically highly expressed in B-cell lymphoma tissues through TMT protein quantitative mass spectrometry detection;

[0009] Figure 2 The figure shows the expression of DNAJC9 in B-cell lymphoma tissues and in various subtypes of lymphoma;

[0010] Figure 3 This is a comparison of the diagnostic capabilities of DNAJC9, CD20 and PAX5 for B-cell lymphoma;

[0011] Figure 4 It is a map of the cellular localization and expression of DNAJC9 in multiple tissues;

[0012] Figure 5 Statistical graph of immunofluorescence staining of pathological sections from patients with inflammatory diseases and reactive lymphoproliferation, extranodal marginal zone lymphoma, and diffuse large B-cell lymphoma using DNAJC9 monoclonal antibody;

[0013] Figure 6 Immunohistochemical staining of DNAJC9 monoclonal antibody on pathological sections of patients with inflammatory diseases and reactive lymphoproliferation, extranodal marginal zone lymphoma, and diffuse large B-cell lymphoma; DETAILED DESCRIPTION

[0014] In order to make the present invention more clearly understood, a preferred embodiment is described in detail with reference to the accompanying drawings as follows:

[0015] like Figure 1-6 As shown; the present invention provides the application of DNAJC9 in preparing a B cell lymphoma diagnostic kit.

[0016] The present invention provides application of DNAJC9 in preparing a differential diagnosis kit for lymphocyte infiltration caused by reactive lymphoid tissue hyperplasia or inflammation.

[0017] like Figure 1As shown, the present invention detected the B-cell lymphoma tumor tissues of 40 patients and the inflammatory tissues of 31 patients by using TMT protein quantitative mass spectrometry. By using limma analysis, logistic regression, lasso regression and stepwise logistic regression analysis, the DnaJ heat shock protein family member C9 (DNAJC9) was screened as a potential differential diagnostic marker specifically expressed in B-cell lymphoma tissue.

[0018] like Figure 2 As shown, DNAJC9 is a heat shock protein that has binding activity to histones and is involved in the positive regulation of nucleosome assembly and ATPase activity. DNAJC9 is significantly overexpressed in B-cell lymphoma tissues and is stably overexpressed in various lymphoma subtypes.

[0019] like Figure 3 As shown in the proteomic data, the diagnostic ability of DNAJC9 for B cell lymphoma is relatively better than the traditional B lymphocyte markers CD20 and PAX5 used for diagnosis.

[0020] like Figure 4 , Figure 5 As shown in the figure, the cellular localization and expression of DNAJC9 in inflammatory tissues, paracancerous tissues, extranodal marginal zone lymphoma (EMZL), and diffuse large B-cell lymphoma (DLBCL) were verified by immunofluorescence staining. It was confirmed that DNAJC9 expression in normal glandular tissues was mainly distributed in the cytoplasm; DNAJC9 was mainly expressed in the nucleus in lymphocytes; and DNAJC9 and CD20 had a high colocalization in lymphoma tissues. The median fluorescence intensity of DNAJC9 in lymphoma tissues was higher than that in inflammatory tissues and paracancerous tissues.

[0021] The above results prove that DNAJC9 is a protein that is specifically and highly expressed in B-cell lymphoma, and its nuclear expression can be used as a pathological diagnostic marker for diagnosing B-cell tumors.

[0022] Example

[0023] DNAJC9 monoclonal antibody was used to immunohistochemically stain pathological sections of 12 patients with inflammatory diseases and reactive lymphoproliferation, 8 patients with extranodal marginal zone lymphoma, and 8 patients with diffuse large B-cell lymphoma (eg, Figure 6 shown).

[0024] The results showed that extranodal marginal zone lymphoma (EMZL) and diffuse large B-cell lymphoma (DLBCL) showed strong nuclear staining of DNAJC9, among which the nuclear staining of DNAJC9 in extranodal marginal zone lymphoma (EMZL) was the strongest.

[0025] The above is only a preferred embodiment of the present invention, and is not any formal or substantial limitation of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the present invention, and these improvements and supplements should also be regarded as the protection scope of the present invention. Any technician familiar with this profession, without departing from the spirit and scope of the present invention, can make some changes, modifications and equivalent changes made by using the technical content disclosed above, which are equivalent embodiments of the present invention; at the same time, any changes, modifications and evolutions of any equivalent changes made to the above embodiments based on the essential technology of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. Application of DNAJC9 protein in the preparation of diagnostic kit for extranodal marginal zone lymphoma.

2. Application of DNAJC9 protein in the preparation of diagnostic kit for diffuse large B-cell lymphoma.