CN110687283A - Use of autoantibodies for diagnosis and/or treatment of tumors - Google Patents
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Abstract
The invention provides an application of a reagent for detecting autoantibody in preparing a tumor and autoimmune disease product for diagnosis, treatment and/or prognosis evaluation, and a marker for diagnosis, treatment and/or prognosis evaluation of tumor or autoimmune disease, wherein the marker is the autoantibody. The expression level of the marker is detected by a rapid double-antibody sandwich enzyme-linked immunosorbent assay (rapid-ELISA), and the curative effect response and the long-term benefit condition of the patient to the tumor immunotherapy are judged or assisted.
Description
Technical Field
The invention relates to the field of biomedical detection, in particular to application of an autoantibody in diagnosis, treatment and prognosis evaluation of tumors or autoimmune diseases, wherein the autoantibody is selected from one or more of CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 or VMAC.
Background
Global disease burden studies by the world health organization show that cancer is a high mortality disease next to cardiovascular disease worldwide and china. Immunotherapy has become an emerging means of cancer treatment by enhancing the immune system of patients to combat disease. In many immunotherapeutic strategies, Immune Checkpoint Inhibitors (ICBs) have shown significant benefit in the treatment of a variety of cancers by blocking the intrinsic down-regulation programs of immunity, such as cytotoxic T lymphocyte antigen 4(CTLA-4) and programmed cell death 1(PD-1) or its ligand (PD-L1), increasing anti-tumor immunity. The advent of ICB has increased the overall survival of patients with a variety of cancers, and a number of inhibitor drugs are currently approved by the U.S. food and drug administration and the chinese food and drug administration for the treatment of malignancies, but clinical results indicate that patients receiving ICB monotherapy in the vast majority of unselected solid tumors have an objective effective rate of only 10% to 30%, and that a majority of patients do not benefit from this, i.e. primary resistance, and that disease progression, i.e. secondary resistance, occurs even after a period of treatment for patients who are therapeutically effective. With the advent of more ICB drugs and the gradual increase of drug-taking population, it is crucial to find effective therapeutic effect prediction markers and establish related prediction models, so that the tumor response rate can be improved, the treatment cost and the time cost can be saved for patients, a personalized diagnosis and treatment strategy can be provided for the treatment of tumor patients, and the life cycle and the life quality of the patients can be improved.
At present, it is known that early tumor cells can express and produce some abnormal proteins, and can produce specific antibodies after being recognized by the immune system of the body, these proteins are called tumor-associated antigens, and the antibodies are called autoantibodies, and the antibodies are relatively more researched in autoimmune diseases, and in recent years, the early tumor cell expression has certain research in the aspects of disease screening, early diagnosis, prognosis judgment and curative effect monitoring, and the early tumor cell expression has great potential. Compared with other markers, the serum autoantibody sampling approach is simple, and continuous sampling and monitoring can be performed in the treatment process, so that the ICB curative effect prediction by using the autoantibody in the serum has certain advantages. In the early research, the SEREX (recombinant cDNA expression library serological screening), phage peptide library panning, SERPA (serum proteomics) and other methods are respectively adopted to screen the tumor autoantibodies, and a batch of published tumor autoantibodies are used for tumor diagnosis at present. Wherein autoantibodies such as NY-SEO-1, p53, Annexin I, 14-3-3 theta, LAMR1, PGP9.5, c-myc, HER2, CAGE, GBU-4-5, SOX2 and the like are used for lung cancer diagnosis; autoantibodies such as p53, HSP70, HCC-22-5, peroxiredoxin VI, KM-HN-1, p90 and the like are used for gastric cancer diagnosis; autoantibodies such as p62 and HCC1 are used for liver cancer diagnosis; autoantibodies such as interleukin-29(IL29), Survivin (SUR), growing hormone (GRH), Osteoprotegerin (OPG), and Resistance (RES) are used for diagnosis of breast cancer. Regarding the relationship between autoantibodies and the effect of ICB treatment, studies have reported that the production of autoantibodies is related to the toxic and side effects of ICB treatment, and the level of autoantibodies has some relationship with the effect of ICB treatment.
Eukaryotic translation initiation factor 4E (EIF 4E) is a cap-binding protein that specifically recognizes the cap structure at the 5' end of mRNA and plays an important role in the initiation of eukaryotic translation. EIF4E is one of factors closely related to malignant tumors, is highly expressed in various human malignant tumors, and is closely related to the occurrence, infiltration and metastasis of tumors. For example: the literature: the expression and significance of EIF4E in liver cancer tissue, Shandong medicine, disclose that the positive expression rate of EIF4E in liver cancer tissue is obviously higher than that of paracancer hardened liver tissue and normal liver tissue, and the expression is irrelevant to the self condition of a patient, the size of tumor and the completion degree of envelope, and is relevant to the differentiation degree of liver cancer, clinical staging and the existence of portal vein cancer embolus, because the expression of EIF4E protein is increased along with the reduction of the differentiation degree of liver cancer, EIF4E can be used for diagnosing and treating liver cancer. Patent CN106460064A discloses a method for determining the prognosis of a patient suffering from high grade serous ovarian cancer (HG-SOC) comprising determining a mutation in the gene ANKHD1-eIF4EBP 3. The literature: the research progress of EIF4E in cervical cancer, modern oncology, discloses that EIF4E is increased in cervical tumor and can promote the expression of HPVE7 protein, and the increase of the tissue malignancy of the cervix is accompanied with the increase of the expression of EIF4E, so that EIF4E is a potential marker for diagnosing and prognosing cervical cancer. However, EIF4E is still low expressed in many tumor diseases, and EIF4E or EIF4E autoantibodies have not been disclosed as a marker for ICB treatment of tumors or autoimmune diseases.
The literature: the expression of the CCDC8 gene in breast cancer, namely the lymphen, tumor research and clinic, adopts quantitative reverse transcription polymerase chain reaction to analyze the expression conditions of the CCDC8 in 40 cases of breast cancer combinations and 22 cases of benign breast tumor tissues, and the result shows that the expression level of the CCDC8 gene in the benign breast tumor of the breast is obviously higher than that of the breast cancer tissues, and the expression has statistical significance. Because the CCDC8 is expressed in breast tumor tissues, the expression level of malignant tissues is lower than that of benign tissues, and the expression of CCDC8 is related to age, lump size and nm23, the CCDC8 is probably an anti-cancer gene of breast cancer and influences the occurrence and development of the breast cancer. The literature: the function research of a new molecule CCDC134, such as Huangjing and the like, proves that the CCDC134 is used as a potential cell factor, plays an important function in tumor immunity and autoimmune diseases through experiments, and has potential application value. The literature: the expression and clinical significance of the CCDC67 gene in thyroid papillary carcinoma, a Master academic paper of Zheng Zhou university in Lei Meng Yuan, analyzes the expression conditions of CCDC67mRNA and protein in differentiated thyroid cancer cell strains through a real-time fluorescent quantitative PCR technology and a cellular immunofluorescence technology, and judges the function of the CCDC67 gene in thyroid tumors. The literature: the effect of silencing DDX49 gene on osteosarcoma cell proliferation, a research biology research thesis of Lanzhou university, discloses that the expression of DDX49 gene is detected to determine the effect of DDX49 gene on osteosarcoma cell proliferation and apoptosis, and provides a new molecular target for diagnosis and treatment of osteosarcoma. However, the above prior arts all use a single autoantibody as a target to serve as a potential marker for diagnosis or prognosis, and the sensitivity and specificity are limited; and the application of the combination of EIF4E2, CCDC130, UBALD1, LPCAT4 and/or VMAC autoantibodies, the combination of FATE1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies and the combination of CPLX2, DDX49, PHACTR1, EIF4E2 and VMAC autoantibodies in the preparation of a product for predicting the curative effect or prognostically evaluating tumors or autoimmune diseases has not been disclosed.
Disclosure of Invention
The inventor successfully detects the levels of CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and VMAC autoantibodies in the blood of a patient with tumor or autoimmune disease by a rapid double-antibody sandwich enzyme-linked immunosorbent assay (rapid-ELISA), and the levels of the autoantibodies in the same serum sample are different.
The invention provides the application of the reagent for detecting the autoantibody in preparing a product for diagnosing, treating and/or prognostically evaluating tumors and autoimmune diseases, and the application of the autoantibody in preparing a product for diagnosing, treating and/or prognostically evaluating tumors and autoimmune diseases.
It is another object of the present invention to provide a marker for the diagnosis, treatment and/or prognostic evaluation of tumor, autoimmune diseases.
It is a further object of the invention to provide a product for the diagnosis, treatment and/or prognostic evaluation of neoplastic, autoimmune and/or autoimmune diseases.
It is still another object of the present invention to provide a method for detecting autoantibodies.
It is a further object of the present invention to provide a method for the diagnosis, treatment and/or prognostic evaluation of neoplastic, autoimmune and/or autoimmune diseases.
In a first aspect of the present invention, there is provided a use of a reagent for detecting an autoantibody in the manufacture of a product for diagnosing and/or treating a tumor or an autoimmune disease, wherein the autoantibody is selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
Preferably, the detection of autoantibodies is the detection of the presence or absence, or the expression level, of autoantibodies.
Preferably, the method for detecting autoantibodies by using the reagent for detecting autoantibodies is one or a combination of two or more of ELISA, rapid-ELISA, immunoblotting, indirect immunofluorescence, enzyme-linked immunosorbent assay, or immunofluorescence.
In a specific embodiment of the present invention, the method for detecting autoantibodies by using the autoantibody detection reagent is rapid-ELISA.
In a second aspect of the present invention, there is provided a use of a reagent for detecting an autoantibody selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor treatment prognosis evaluation is prognosis evaluation after treatment by using an immune checkpoint inhibitor, or after combination of the immune checkpoint inhibitor and other medicaments and treatment means such as radiotherapy, chemotherapy and the like.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
Preferably, the detection of autoantibodies is the detection of the presence or absence, or the expression level, of autoantibodies.
Preferably, the method for detecting autoantibodies by using the reagent for detecting autoantibodies is one or a combination of two or more of ELISA, rapid-ELISA, immunoblotting, indirect immunofluorescence, enzyme-linked immunosorbent assay, or immunofluorescence.
In a specific embodiment of the present invention, the method for detecting autoantibodies by using the autoantibody detection reagent is rapid-ELISA.
In a third aspect of the present invention, there is provided a use of an autoantibody in the manufacture of a product for diagnosing and/or treating a tumor or an autoimmune disease, said autoantibody being selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
In a fourth aspect of the invention, there is provided a use of an autoantibody in the manufacture of a product for prognosis of treatment of a tumour or autoimmune disease, said autoantibody being selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the prognosis of tumor treatment is evaluated by using an immune checkpoint inhibitor, or by using a combination of an immune checkpoint inhibitor and other drugs, radiotherapy, chemotherapy, and the like.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
In a fifth aspect of the present invention, there is provided a marker for diagnosing and/or treating tumor and autoimmune diseases, wherein the marker comprises an autoantibody selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
In a specific embodiment of the invention, the marker may further comprise other immune checkpoint proteins or autoantibodies thereof other than CPLX2, DDX49, PHACTR1, FATE1, ubad 1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies as concomitant markers for the detection of the therapeutic effect of a tumor or autoimmune disease in combination with CPLX2, DDX49, PHACTR1, FATE1, ubad 1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies. Wherein the concomitant marker is one or the combination of more than two of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD 160.
In a sixth aspect of the present invention, there is provided a marker for prognosis evaluation of treatment of a tumor or an autoimmune disease, the marker comprising an autoantibody selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the prognosis evaluation of tumor treatment is prognosis evaluation after treatment with an immune checkpoint inhibitor, or after treatment with a combination of an immune checkpoint inhibitor and other drugs and treatment means such as radiotherapy and chemotherapy.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
In a specific embodiment of the invention, the marker may further comprise other immune checkpoint proteins or autoantibodies thereof other than CPLX2, DDX49, PHACTR1, FATE1, ubad 1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies as concomitant markers for prognostic assessment of treatment of tumor or autoimmune disease in combination with CPLX2, DDX49, PHACTR1, FATE1, ubad 1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies. Wherein the concomitant marker is one or the combination of more than two of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD 160.
In a seventh aspect of the present invention, there is provided a product for diagnosing and/or treating tumors and autoimmune diseases, said product comprising a reagent for detecting autoantibodies, said autoantibodies being selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
Preferably, the detection of autoantibodies is the detection of the presence or absence, or the expression level, of autoantibodies.
Preferably, the method for detecting autoantibodies by using the reagent for detecting autoantibodies is one or a combination of two or more of ELISA, rapid-ELISA, immunoblotting, indirect immunofluorescence, enzyme-linked immunosorbent assay, or immunofluorescence.
In a specific embodiment of the present invention, the method for detecting autoantibodies by using the autoantibody detection reagent is rapid-ELISA.
Preferably, the product for diagnosing and/or treating tumor and autoimmune diseases may further comprise other immune checkpoint proteins or autoantibodies thereof other than CPLX2, DDX49, phact 1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies as concomitant markers, in combination with CPLX2, DDX49, phact 1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies, for detecting the therapeutic effect of tumor and autoimmune diseases. Wherein the concomitant marker is one or the combination of more than two of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD 160.
In an eighth aspect of the present invention, there is provided a product for prognosis evaluation of treatment of tumor or autoimmune disease, said product comprising a reagent for detecting autoantibody, said autoantibody being selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
Preferably, the detection of autoantibodies is the detection of the presence or absence, or the expression level, of autoantibodies.
Preferably, the method for detecting autoantibodies by using the reagent for detecting autoantibodies is one or a combination of two or more of ELISA, rapid-ELISA, immunoblotting, indirect immunofluorescence, enzyme-linked immunosorbent assay, or immunofluorescence.
In a specific embodiment of the present invention, the method for detecting autoantibodies by using the autoantibody detection reagent is rapid-ELISA.
Preferably, the product for prognosis evaluation of tumor or autoimmune disease treatment may further comprise other immune checkpoint proteins or autoantibodies thereof other than CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies as concomitant markers in combination with CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies for detection of prognosis evaluation of tumor or autoimmune disease treatment. Wherein the concomitant marker is one or the combination of more than two of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD 160.
In a ninth aspect of the invention, there is provided a method for diagnosing a neoplastic or autoimmune disease, said method comprising detecting the presence or level of expression of an autoantibody selected from the group consisting of:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
In a tenth aspect of the present invention, there is provided a method for prognosis evaluation of treatment of a tumor or an autoimmune disease, the method comprising detecting the presence or the expression level of an autoantibody selected from one of the following groups in an organism:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the autoantibodies are in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the invention, the autoantibodies are in serum and/or plasma.
In an eleventh aspect of the invention, there is provided a method of treatment of a tumour or an autoimmune disease, said method comprising administering to a patient having a tumour an effective amount of an immune checkpoint inhibitor, or a combination of an immune checkpoint inhibitor and another drug and a treatment modality such as radiotherapy or chemotherapy, wherein expression of autoantibodies is detected in the patient, said autoantibodies being selected from one of the following:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
In one embodiment of the invention, the tumor is a lymphoma.
Preferably, the immune checkpoint inhibitor is selected from the group consisting of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD160 inhibitors.
Preferably, the detection of autoantibody expression in the patient is detection of autoantibody expression in serum, plasma, interstitial fluid, cerebrospinal fluid or urine of the patient. Wherein, the higher the expression level of the autoantibody is, the better the effect of the immune checkpoint inhibitor or the combined treatment by adopting the immune checkpoint inhibitor and other medicines and treatment means such as chemotherapy and radiotherapy.
In a particular embodiment of the invention, the detection of autoantibody expression from the patient is the detection of autoantibody expression from the patient's serum and/or plasma.
In a twelfth aspect of the present invention, there is provided a method for detecting an autoantibody, comprising coating a carrier surface with a corresponding protein, adding a sample to be detected, adding an enzyme and a substrate, and measuring the concentration.
Preferably, the autoantibody is selected from CPLX2, DDX49, phatcr 1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4, and/or VMAC.
Preferably, the autoantibody comprises one or a combination of two or more of autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD.
Preferably, the sample to be tested is biological serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
In one embodiment of the present invention, the sample to be tested is biological serum.
Preferably, the sample to be detected is diluted by a dilution buffer before being added, and the dilution concentration is 1: 100-1000.
More preferably, the dilution concentration is 1: 150-500.
Preferably, the dilution concentration is 1: 200-400.
In one embodiment of the present invention, the dilution buffer is milk; the milk is PBST diluted milk.
Preferably, the enzyme is an enzyme-labeled antibody. More preferably, the enzyme-labeled antibody is IgG.
In one embodiment of the invention, the substrate is TMB.
Preferably, the method for measuring the concentration is to measure the absorbance value at 450 nm.
In one embodiment of the present invention, the method comprises:
1) coating the capture antibody in a 96-well plate, keeping the temperature at4 ℃ overnight, and washing; diluting with milk, and sealing for 1-3 hr; preferably, the mixture is sealed for 2 hours after being diluted by milk;
simultaneously adding the corresponding plasmid into an in vitro expression system, reacting for 1-3h, preferably 2h, in a dark place, diluting with milk, adding into a 96-well plate, washing at room temperature for 0.5-2h, preferably 1h, preferably, wherein the in vitro expression system is IVTT; preferably, the serum sample is diluted to 1:200-400 with milk;
2) adding the diluted serum sample into a 96-well plate, incubating and washing; preferably the incubation time is 0.5-2 hours;
3) adding a fresh diluted anti-human IgG HRP enzyme-labeled antibody, incubating and washing; preferably the incubation time is 0.5-2 hours; more preferably the incubation time is 0.5-1 hour;
4) adding a TMB substrate which is prepared temporarily, and developing in a dark place; adding sulfuric acid to terminate the reaction; preferably, the dark color development time is 10-30 minutes;
5) the level of autoantibody expression in the sample is determined by measuring the absorbance at 450 nm.
The reagent for detecting the expression level of the autoantibody is selected from test paper strips, protein chips, magnetic beads, fluorescent reagents and the like. The detection principle adopts antigen-antibody combination, wherein the detection antigen is protein, polypeptide or antibody.
The product of the invention comprises the reagent for detecting the level of the autoantibody of the invention. Preferably, the product is selected from the group consisting of a kit and mass spectrometry.
A kit for detecting autoantibodies comprising reagents for detecting autoantibody levels.
A chip for detecting autoantibodies, comprising a reagent for detecting the level of autoantibodies.
A kit for diagnosing and/or treating a tumor comprising reagents for detecting CPLX2, DDX49, phatcr 1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4, and/or VMAC autoantibody levels and reagents for detecting other immune checkpoints. The other immune check points are selected from one or more than two of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD 160. Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor. In one embodiment of the invention, the tumor is a lymphoma.
A kit for prognosis evaluation of tumor treatment comprising reagents for detecting CPLX2, DDX49, phatcr 1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4, and/or VMAC autoantibody levels and reagents for detecting other immune checkpoints. The other immune check points are selected from one or more than two of PD-1, PD-L1, CTLA-4, BTLA, TIM-3, LAG-3, TIGIT, LAIR1, 2B4 or CD 160. Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor. In one embodiment of the invention, the tumor is a lymphoma.
The diagnosis of tumor in the invention refers to the diagnosis of whether tumor is suffered or not, or the prognosis evaluation of tumor patients, or the evaluation of the benefit degree of the tumor patients treated by immune checkpoint inhibitor.
The tumor treatment according to the present invention is to determine whether to treat by immune checkpoint inhibitors by detecting the expression level of CPLX2, DDX49, phatcr 1, FATE1, ubad 1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibodies.
The tumor of the invention is selected from lymphoma, non-small cell lung cancer, leukemia, ovarian cancer, breast cancer, endometrial cancer, colon cancer, rectal cancer, gastric cancer, bladder cancer, lung cancer, bronchial cancer, bone cancer, prostate cancer, pancreatic cancer, liver and bile duct cancer, esophageal cancer, kidney cancer, thyroid cancer, head and neck cancer, testicular cancer, glioblastoma, astrocytoma, melanoma, myelodysplastic syndrome, and sarcoma. Wherein the leukemia is selected from acute lymphocytic (lymphoblastic) leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, plasma cell leukemia, and chronic myelogenous leukemia; said lymphoma is selected from Hodgkin's lymphoma and non-Hodgkin's lymphoma, including B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone B-cell lymphoma, T-cell lymphoma, and Waldenstrom's macroglobulinemia; the sarcoma is selected from osteosarcoma, Ewing's sarcoma, leiomyosarcoma, synovial sarcoma, soft tissue sarcoma, angiosarcoma, liposarcoma, fibrosarcoma, rhabdomyosarcoma, and chondrosarcoma. Preferably, the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor. In one embodiment of the invention, the tumor is a lymphoma.
The autoimmune disease of the present invention is selected from organ-specific autoimmune diseases and systemic autoimmune diseases. Wherein the organ-specific autoimmune disease is selected from chronic lymphocytic thyroiditis, hyperthyroidism, insulin-dependent diabetes mellitus, myasthenia gravis, ulcerative colitis, pernicious anemia with chronic atrophic gastritis, goodpasture's syndrome, pemphigus vulgaris, pemphigoid, primary biliary cirrhosis, multiple sclerosis, acute idiopathic polyneuritis, etc. The systemic autoimmune disease is selected from systemic lupus erythematosus, rheumatoid arthritis, cutaneous rheumatoid nodules, arteritis, pericarditis, scleritis, lymphadenitis, hepatosplenomegaly, neuropathy, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, autoimmune hemolytic anemia, thyroid autoimmune disease or ulcerative colitis.
Drawings
Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1: the rapid-ELISA sandwich method is used for detecting the distribution of serum EIF4E2 autoantibodies of 117 tumor patients, and the specific tumor patients comprise lymphoma, lung cancer and soft tissue sarcoma.
FIG. 2: distribution of EIF4E2 autoantibodies between an immunotherapeutically effective group and an ineffective group, wherein the effective group is a tumor immunotherapeutically effective group, i.e., a responsive group, and the ineffective group is a tumor immunotherapeutically ineffective group, i.e., a non-responsive group.
FIG. 3: ROC curve of prediction of the effect of EIF4E2 autoantibodies on the efficacy of immunotherapy.
FIG. 4: ELISA sandwich method for detecting the comparison of the relative levels of EIF4E2, CCDC130, UBALD1, LPCAT4 and VMAC autoantibody in the serum of lymphoma patients.
FIG. 5: ROC curves for predicting the efficacy of EIF4E2, CCDC130, UBALD1, LPCAT4, VMAC five autoantibodies in combination with immunotherapy in 57 lymphoma training set patients.
FIG. 6: prediction of long-term survival of patients immunized with 57 lymphoma training set patients by the combination of five autoantibodies, EIF4E2, CCDC130, UBALD1, LPCAT4, VMAC.
FIG. 7: EIF4E2, CCDC130, UBALD1, LPCAT4 and VMAC five autoantibodies are combined to verify ROC curves of curative effect prediction of immunotherapy of 32 lymphoma test set patients.
FIG. 8: ELISA sandwich method for detecting the comparison of the relative levels of EIF4E2, CCDC130, FATE1, LPCAT4 and VMAC autoantibody in the serum of lymphoma patients.
FIG. 9: ROC curves for predicting the curative effect of EIF4E2, CCDC130, FATE1, LPCAT4 and VMAC five autoantibodies in combination on immunotherapy of 57 lymphoma training set patients.
FIG. 10: prediction of long-term survival of patients immunized with 57 lymphoma training set patients by the combination of five autoantibodies, EIF4E2, CCDC130, FATE1, LPCAT4, and VMAC.
FIG. 11: the validation ROC curve of the prediction of the curative effect of EIF4E2, CCDC130, FATE1, LPCAT4 and VMAC five autoantibodies in combination on the immunotherapy of 32 lymphoma test set patients.
FIG. 12: ELISA sandwich method for detecting comparison of relative levels of CPLX2, EIF4E2, DDX49, PHACTR1 and VMAC autoantibody in serum of lymphoma patients.
FIG. 13: ROC curves for predicting the efficacy of CPLX2, EIF4E2, DDX49, phatcr 1, VMAC five autoantibodies in combination with immunotherapy in 57 lymphoma training set patients.
FIG. 14: CPLX2, EIF4E2, DDX49, PHACTR1, VMAC five autoantibodies in combination with prediction of long-term survival in patients with immunotherapy from 57 lymphoma training set patients.
FIG. 15: validation ROC curve of prediction of curative effect of CPLX2, EIF4E2, DDX49, PHACTR1 and VMAC five autoantibodies in combination on immunotherapy of 32 lymphoma test set patients.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
1. Sample collection
Serum samples were collected at the national academy of medicine tumor hospital with a median age of 34(18-74) years of age and a male to female ratio of 71:46, 89 of lymphoma patients, 16 of non-small cell lung cancer patients, 12 of soft tissue sarcoma patients, all of whom received informed consent. And (4) confirming the tumor diagnosis result through the pathological result, receiving the PD-1 antibody immunotherapy on all patients, and obtaining the curative effect evaluation information.
Of the 89 lymphoma patients, the median age was 34(18-69) years, the male-female ratio was 52:37, and the grouping was as follows:
1) according to the evaluation criteria of the curative effect of the solid tumor (RECIST 1.1), the curative effect of the lymphoma is divided into four grades, namely CR (complete remission), PR (partial remission), SD (stable disease), PD (progressive disease) and the curative effect is reduced in sequence. To evaluate the correlation between the efficacy of autoantibodies and immunotherapy in lymphoma patients, in combination with the previously reported literature and actual efficacy, patients with 3(CPLX2, EIF4E2, DDX49, phatr 1, VMAC), 4.5(EIF4E2, CCDC130, FATE1, LPCAT4, VMAC), 6(EIF4E2, CCDC130, ubad 1, LPCAT4, VMAC) continued CR, PR, SD within months, while patients with PD within 3 months were placed in the active group.
2) 89 patient sera were randomly assigned to the training set (57 cases) and the test set (32 cases).
2. Detection method
Detecting protein: CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4, and/or VMAC
The method comprises the following steps: a rapid enzyme-linked immunosorbent assay (rapid-ELISA) was performed to assess the concentration of serum autoantibodies. Capture antibody IgG, anti-GST antibody (10 ng/. mu.l. times.50. mu.l) was coated in 96-well plates, washed after overnight at4 ℃, blocked with 50. mu.l of PBST-diluted milk buffer (milk 5%, tween 0.2%) for 2 hours, while the corresponding plasmid (1 ng/. mu.l. times.50. mu.l) was coated in 96-well plates, washed after overnight at4 ℃, added to the in vitro expression system IVTT, protected from light at 37 ℃ for 1.5 hours, diluted with milk, added to 96-well plates, washed after 1 hour reaction at room temperature. Serum samples were diluted in dilution buffer (1: 300 dilution concentration) and 50. mu.L of diluted sample/well was added to a 96-well microtiter plate, incubated at 37 ℃ for 1 hour, and then washed. 50. mu.L of a freshly diluted anti-human IgG HRP enzyme-labeled antibody (diluted 1: 8000) was added to each reaction well, incubated at 37 ℃ for 1 hour, and washed. Then, 0.1mL of the temporarily prepared TMB substrate solution was added to each reaction well, and the reaction was quenched by adding 50. mu.L of 0.05M sulfuric acid to each well, and developed in the dark at 37 ℃ for 25 minutes, and the signal was determined by measuring the absorbance at 450 nm.
3. Statistical analysis
Differences in the variables between groups were compared using the Mann-Whitney U Test, and P <0.05 was considered statistically significant.
4. Results of the experiment
1) The method can successfully detect the level of autoantibody in the serum of tumor patients
The EIF4E2 autoantibody expression level of 89 lymphoma, 16 non-small cell lung cancer and 12 serum samples of soft tissue sarcoma patients was tested by using the conditions of the above ELISA, and the EIF4E2, CCDC130, UBALD1, LPCAT4, VMAC five autoantibody levels, EIF4E2, CCDC130, FATE1, LPCAT4 and VMAC five autoantibody levels and CPCX 2, EIF4E2, DDX49, PHACTR1 and VMAC five autoantibody levels of 89 tumor patients were tested at the same time. The results show that the relative level of autoantibodies in the serum of tumor patients, the level of EIF4E2 autoantibodies in the serum of patients with different tumors (see FIG. 1), the level of EIF4E2, CCDC130, UBALD1, LPCAT4, VMAC five autoantibodies (see FIG. 4), EIF4E2, CCDC130, FATE1, LPCAT4, VMAC five autoantibodies (see FIG. 8), CPLX2, EIF4E2, DDX49, PHACTR1 and VMAC five autoantibodies (see FIG. 12) are different by using the above enzyme-linked immunosorbent assay, and the level of autoantibodies in the serum of patients is different.
2) Relationship between serum autoantibody level of tumor patients and curative effect of immunotherapy
The more effective differentiation between effective and ineffective patients in tumor immunotherapy is a major challenge to be solved in the clinic, and therefore, the OD values were first standardized and the relationship between the serum CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and/or VMAC autoantibody levels of lymphoma patients and PD1 immunotherapy was examined.
Analysis of the individual indices EIF4E 2: the results of the analysis of 89 lymphoma patients are shown in FIG. 2, and show that the level of EIF4E2 autoantibodies was higher in the treatment-effective patients than in the non-responsive group.
Analysis of five kinds of autoantibodies, EIF4E2, CCDC130, UBALD1, LPCAT4, VMAC: the results of the analyses performed on the training set of 57 patients are shown in FIG. 5, where the serum autoantibody levels in lymphoma patients combined with the ability to predict PD-1 immunotherapy reached an area under the curve of 0.75. Further, as shown in FIG. 6, the survival status of the effective and ineffective patients predicted by the combined index in 57 patients was found to be longer, indicating that the combination of the five autoantibodies has a certain long-term prognosis.
Analysis of five kinds of autoantibodies, EIF4E2, CCDC130, FATE1, LPCAT4, VMAC: the results of the analyses performed on the training set of 57 patients are shown in FIG. 9, where the serum autoantibody levels in lymphoma patients combined with the ability to predict PD-1 immunotherapy reached an area under the curve of 0.73. Further, as shown in FIG. 10, the survival status of the effective and ineffective patients predicted by the combined index in 57 patients was found to be longer, indicating that the combination of the five autoantibodies has a certain long-term prognosis.
Analysis of five autoantibodies, CPLX2, EIF4E2, DDX49, PHACTR1, VMAC: the results of the analyses performed on the training set of 57 patients are shown in FIG. 13, where the serum autoantibody levels in lymphoma patients combined with the ability to predict PD-1 immunotherapy reached an area under the curve of 0.77. Further, as shown in FIG. 14, the survival status of the effective and ineffective patients predicted by the combined index in 57 patients was found to be longer, indicating that the combination of five autoantibodies has a certain long-term prognosis.
3) ROC curve of efficacy prediction of autoantibodies for immunotherapy.
When the EIF4E2 index is used alone to distinguish patients with different curative effects, the area under the curve can reach 0.73 (see figure 3). The results of verifying 32 test set patients by using the combination of five kinds of autoantibodies, namely EIF4E2, CCDC130, UBALD1, LPCAT4 and VMAC are shown in figure 7, the effect of the combination detection of the five kinds of autoantibodies on the prediction of the curative effect of the lymphoma immunotherapy is verified, and the area under the curve can reach 0.70. The results of the verification of 32 test set patients by using the combination of five kinds of autoantibodies, namely EIF4E2, CCDC130, FATE1, LPCAT4 and VMAC are shown in figure 11, the effect of the combination detection of the five kinds of autoantibodies on the prediction of the curative effect of the lymphoma immunotherapy is proved, and the area under the curve can reach 0.62. Five autoantibodies CPLX2, EIF4E2, DDX49, PHACTR1 and VMAC were used in combination to verify 32 test set patients, and the results are shown in FIG. 15, which confirms the effect of the five autoantibodies in combination detection for predicting the curative effect of lymphoma immunotherapy, and the area under the curve can reach 0.69. Therefore, the serum CPLX2, DDX49, PHACTR1, FATE1, UBALD1, EIF4E2, CCDC130, LPCAT4 and VMAC autoantibody level are potential tumor immunotherapy markers.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
Claims (10)
1. Use of a reagent for detecting autoantibodies in the manufacture of a product for the diagnosis and/or treatment of neoplastic and autoimmune diseases, wherein the autoantibodies are selected from one of the group consisting of:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
2. the use of claim 1, wherein the detection of autoantibodies is the detection of the presence or absence, or the level of expression, of autoantibodies; the autoantibody comprises one or more than two of subtype IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD of the autoantibody; the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor.
3. The use according to claim 2, wherein the autoantibody detection reagent is used in a method selected from the group consisting of ELISA, rapid-ELISA, immunoblotting, indirect immunofluorescence, enzyme immuno-spotting, and immuno-luminescence.
4. Use of a reagent for detecting autoantibodies for the manufacture of a product for the prognosis of a tumour or autoimmune disease, wherein the autoantibodies are selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
5. the use of claim 4, wherein the autoantibody comprises one or a combination of two or more of the autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD; the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor; the treatment prognosis evaluation of the tumor is the prognosis evaluation after the treatment by adopting an immune checkpoint inhibitor or the combination treatment of the immune checkpoint inhibitor, other medicines, radiotherapy and chemotherapy treatment means.
6. Use of an autoantibody for the manufacture of a product for the diagnosis and/or treatment of a tumour, an autoimmune disease, wherein the autoantibody is selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
7. the use of any one of claims 1 to 6, wherein the autoantibody comprises one or a combination of two or more of the autoantibody subtypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgE or IgD; the tumor is selected from lymphoma, non-small cell lung cancer or soft tissue sarcoma tumor; the autoantibody is in serum, plasma, interstitial fluid, cerebrospinal fluid or urine.
8. A marker for the diagnosis and/or treatment of a tumor, an autoimmune disease, comprising an autoantibody selected from the group consisting of:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
9. a product for the diagnosis and/or treatment of neoplastic, autoimmune or autoimmune diseases, comprising reagents for the detection of autoantibodies selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
10. a detection method of an autoantibody is characterized in that a corresponding protein of the autoantibody is coated on the surface of a carrier, a sample to be detected is added, an enzyme and a substrate are added, and the concentration is measured, wherein the autoantibody is selected from one of the following groups:
(1)EIF4E2；
(2)EIF4E2、CCDC130、UBALD1、LPCAT4、VMAC；
(3)EIF4E2、CCDC130、FATE1、LPCAT4、VMAC；
(4)CPLX2、DDX49、PHACTR1、EIF4E2、VMAC；
(5)EIF4E2、CCDC130、LPCAT4、VMAC；
(6)UBALD1；
(7)FATE1；
(8)EIF4E2、UBALD1；
(9)EIF4E2、FATE1；
(10)CPLX2、DDX49、PHACTR1；
(11)EIF4E2、VMAC。
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| CN116854817A (en) * | 2023-07-10 | 2023-10-10 | 华中农业大学 | Nano antibody targeting eIF4E2, E3 ligase chimeric and application thereof in ISGylation activation |
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