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

IF 5.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
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
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引用次数: 0

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.

COX7A1的过表达促进胃癌对奥沙利铂的耐药性并削弱免疫疗法的疗效
胃癌(GC)是全球最常见的临床恶性肿瘤之一,发病率和死亡率都很高。目前,免疫疗法的总体反应率较低,而目前预测胃癌预后的方法也不尽人意。因此,需要准确、高效、稳定、性能比高且能广泛应用于临床的新型生物标志物。基于中山大学肿瘤防治中心的化疗队列和免疫治疗队列的公开数据集,进行了一系列生物信息学分析,如差异表达分析、生存分析、药物敏感性预测、富集分析、肿瘤免疫功能障碍和排斥(TIDE)分析、单样本基因组富集分析(ssGSEA)、干性指数计算、免疫细胞浸润分析等,进行了筛选和初步探索。免疫组化染色和体外实验则是为了进一步验证。COX7A1的过表达促进了GC细胞对奥沙利铂的耐药性。COX7A1可能通过调节成纤维细胞的数量及其与免疫细胞的细胞通讯诱导免疫逃逸。总之,在临床上测量 COX7A1 的表达水平可能有助于预测 GC 患者的预后、化疗耐药程度和免疫疗法的疗效。
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来源期刊
Laboratory Investigation
Laboratory Investigation 医学-病理学
CiteScore
8.30
自引率
0.00%
发文量
125
审稿时长
2 months
期刊介绍: Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.
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