Application of ARID1B gene variation in prediction of sensitivity of lung adenocarcinoma patients to immune checkpoint inhibitor therapy
An immune checkpoint and gene mutation technology, applied in the field of clinical molecular diagnostics, can solve problems such as the lack of research on lung adenocarcinoma subdivision, achieve the effects of reducing detection costs, accurate prediction results, and improving detection efficiency
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Embodiment 1
[0081] A total of 2859 LUAD patients participated in this study. The characteristics of the patients are shown in Table 1. The male to female ratio is basically 1:1, and the median age at diagnosis is 59 years. Among them, there were 939 cases (32.8%) in stage I, 229 cases (8%) in stage II, 437 cases (15.3%) in stage III, and 1041 cases (36.4%) in stage IV. TMB detection was performed on 2859 patients. The median TMB of the whole population was 3.8muts / Mb (IQR, 1.5-7.7). Tumors with TMB≥10muts / Mb accounted for 19.2%. We found a positive correlation (p<0.001) between age and TMB. In addition, TMB values were higher in the male patient group (p<0.001) as well as in the squamous cell carcinoma patient group (p<0.001).
[0082] Table 1. Characterization of LUAD patients
[0083]
Embodiment 2
[0084] Example 2 The frequency of pathogenic ARID1B mutations in the Chinese LUAD population and its correlation with the immunotherapy biomarker TMB
[0085] Thirty of 2859 LUAD patients carried mutations in the ARID1B gene, accounting for 1%. There was no significant difference in the age, gender, and disease stage ratio between the ARID1B gene variant and the wild type patients (Table 2). The TMB of patients with ARID1B gene mutation was significantly higher than that of ARID1B wild-type patients (median TMB: 9.6vs.3.8, pfigure 1 ).
[0086] ARID1B mutation sites are relatively scattered, and there is no obvious hotspot mutation area ( figure 2 ). There was no significant correlation between ARID1B mutations and PD-L1 expression levels ( image 3 ).
[0087] Table 2. Correlation between ARID1B mutations and clinicopathological features in NSCLC patients
[0088]
Embodiment 3
[0089] Example 3 Validation of clinical data of ARID1B gene variation as an immunotherapy biomarker
[0090] To further validate the predictive value of ARID1B mutations for treatment with immune checkpoint inhibitors (ICIs), we performed external validation by downloading cohort information from public databases. We downloaded the cohort data uploaded by Rizvi et al. from the cBioPortal website (http: / / www.cbioportal.org / ). The Rizvi cohort included 240 patients who received anti-PD-(L)1 monotherapy or anti-PD-(L) 1+anti-CTLA-4 combination therapy for patients with non-small cell lung cancer, the specific patient baseline information can refer to the literature (Liu S-y, Dong Z-y, Wu S-p et al. Clinical relevance of PD-L1expression and CD8+T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer. Lung Cancer 2018;125:86-92). Among the 240 patients, there were 186 patients with lung adenocarcinoma, including 6 patients with ARID1B mutation (3.2%). The...
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