Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy

COX7A1过表达促进胃癌对奥沙利铂耐药并削弱免疫治疗疗效

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作者:Si-Yu Wang, Xian-Qi Yang, Yu-Xin Wang, Ao Shen, Cheng-Cai Liang, Run-Jie Huang, Un Hio Cheng, Rui Jian, Nan An, Yu-Long Xiao, Li-Shuai Wang, Yin Zhao, Chuan Lin, Chang-Ping Wang, Zhi-Ping Yuan, Shu-Qiang Yuan

Abstract

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

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