CN-116449009-B - Autoantibody marker for predicting immune neoadjuvant therapeutic effect of patients with lung cancer in third stage

Abstract

The invention provides an autoantibody marker for predicting the lung cancer immune new auxiliary treatment effect of a lung cancer patient in the third period, a series of autoantibody marker molecules are screened to have great correlation with the lung cancer immune new auxiliary treatment effect prediction by detecting autoantibodies aiming at different antigen targets in the blood of the lung cancer patient in the third period, and 3 autoantibody biomarkers with better lung cancer immune new auxiliary treatment effect prediction efficacy of the lung cancer patient in the third period are further screened and obtained by combining with a CART decision tree strategy, and the combination of the autoantibody biomarkers can be used for efficiently predicting whether the lung cancer immune new auxiliary treatment of the lung cancer patient in the third period is effective or not, provides a reference basis for a clinician to determine a treatment scheme, provides a new prediction means for the lung cancer immune new auxiliary treatment effect of the lung cancer patient in the third period, and has important scientific significance and clinical application value.

Inventors

• SUN SUPENG
• KANG MEIHUA
• WU JIANHU
• YIN LIANG
• ZHU DEKUN
• ZHOU XINGYU
• SUN LIPING

Assignees

• 上海秤信生物科技有限公司

Dates

Publication Date

20260508

Application Date

20230130

Claims (3)

1. 1. A system for predicting whether lung cancer immune neoadjuvant therapy of a patient in a third stage of lung cancer is effective is characterized by comprising a data analysis module, wherein the data analysis module is used for analyzing the detection condition of an autoantibody marker, the autoantibody marker is PBRM1, or comprises a combination of TRIM21 and PBRM1, or comprises a combination of PBRM1 and SS18, or comprises a combination of PBRM1, SS18 and TRIM21, the analysis method of the data analysis module is that whether the autoantibody marker in a blood sample of the patient in the third stage of lung cancer is positive is detected, and the data analysis module evaluates whether lung cancer immune neoadjuvant therapy of the patient in the third stage of lung cancer is effective by analyzing whether the autoantibody marker is positive.
2. 2. The system of claim 1, wherein the analysis means further comprises means for predicting that the immune neoadjuvant therapy for lung cancer is effective in the patient with the third stage lung cancer when one or more of the combinations of autoantibody markers is positive, and means for predicting that the immune neoadjuvant therapy for lung cancer is not effective in the patient with the third stage lung cancer when all of the autoantibodies in the combination of autoantibody markers are negative.
3. 3. The use of an autoantibody marker for the preparation of a reagent for predicting whether an immune neoadjuvant treatment for lung cancer is effective in a patient with third stage lung cancer, characterized in that the autoantibody marker is PBRM1.

Description

Autoantibody marker for predicting immune neoadjuvant therapeutic effect of patients with lung cancer in third stage The present application is a divisional application of the parent application 202310044847.9. Technical Field The invention relates to the technical field of biology, in particular to a biomarker related to a lung cancer immune novel auxiliary treatment effect, and especially relates to an autoantibody marker for predicting a lung cancer immune novel auxiliary treatment effect of a lung cancer patient in third-stage lung cancer. Background Excision of primary tumors is an essential treatment for lung cancer, but surgery itself may also promote postoperative recurrence by inducing perioperative micrometastasis spreading, clearing anti-angiogenic signals from the tumor, inducing secretion of tumor growth factors, and inducing postoperative cell-mediated immunosuppression. Therefore, the tumor cell vitality in the micrometastasis range is reduced, and the early intervention type new auxiliary treatment becomes an attractive treatment strategy, and the strategy can improve the complete control rate of tumor patients before operation, so that the long-term survival and cure rate of the patients can be improved to a great extent. The activation of T cell viability by immune checkpoint inhibitors in neoadjuvant therapy is of great significance, and can lead regulatory T cells to increase, natural killer cells to decrease and the like in non-small cell lung cancer (NSCLC) tumor tissues to form an immunosuppressive tumor microenvironment. The antitumor effect generated by the preoperative immunity novel adjuvant therapy can not only shrink the tumor but also maximize the antitumor effect of the activated organism before the surgical lymph node cleaning. After the main focus is resected, the activated T cells can still eliminate the potential transfer lesions by 'memory' fixed points, thereby improving the cure rate. The conference of the European oncology medical society in 2016 (European Society for Medical Oncology, ESMO) has reported the results of a clinical study of 21 resectable NSCLC patients using an immunological neoadjuvant for the first time. The article published in the journal of new england medicine in 2018 shows good therapeutic safety. For NSCLC patients who can be treated by surgery, no matter whether the driver gene mutation exists or not, 3mg/kg (1 times every 2 weeks and 2 times) of PD-1 inhibitor Nivolumab is used for new adjuvant therapy before surgery, the tolerance is good, unexpected toxic and side effects do not occur, and the patients are not found to delay the treatment time of surgery due to the use of immune checkpoint inhibitor. The study found that the treatment-related adverse effect was 23% and that there were only 1 case of pneumonia with adverse effects exceeding grade 3. In terms of efficacy, 10% (2/20) of patients achieved Partial Response (PR), 86% (18/20) of patients achieved Stable Disease (SD), disease control rate (disease control rate, DCR) up to 96%, and postoperative major pathology-relieving MPR (surviving cells < 10%) up to 45% (9/20), with complete pathology-relieving (pCR) of 5% (3/20). The world lung cancer meeting and ESMO meeting in 2018 report various clinical test results of NEOSTAR, NADIM, LCMC, MAC and the like on application of immune checkpoint inhibitors to NSCLC neoadjuvant therapy. The research of the novel adjuvant immune therapy of the lung cancer which can be subjected to surgical excision shows relatively optimistic data initially, and shows that the novel adjuvant immune therapy of the lung cancer has good application prospect for improving prognosis of patients. However, although lung cancer immunoneoadjuvant therapy has achieved remarkable results, there are data that indicate that some lung cancer patients still have no benefit from it. For example, a substantial proportion of lung cancer patients do not respond to anti-PD-1/PD-L1 antibodies. Therefore, the lung cancer immune new adjuvant therapy also has beneficiary groups and non-beneficiary groups. The current data show that the overall efficacy of lung cancer immune neoadjuvant therapy varies greatly, and it is not clear which populations will benefit from lung cancer immune neoadjuvant therapy. Therefore, the effective biomarker has important significance for selecting lung cancer immune new adjuvant therapy crowd. Immunotherapeutic markers in general cannot be used for the prediction of the efficacy of immune neoadjuvant therapy of lung cancer. CHECKMATE 159A 159 study included 21 resectable NSCLC patients receiving neoadjuvant treatment with NA Wu Liyou mab. The results suggest that tumor MPR was observed at the initial diagnosis regardless of tumor cell PD-L1 expression. 181 resectable NSCLC patients were included in LCMC3 (NCT 02927301) study, and no baseline/intraoperative Tumor Mutational Burden (TMB) correlation with MPR was found in patients receiving 2 cycles of atiliz