Unraveling the role of PREX2 mutations as a biomarker for immunotherapy response in colorectal cancer.

IF 1.9
Huan Peng, Pengmin Yang, Xintao Wang, Xiaokai Zhao, Jieyi Li, Ziying Gong, Daoyun Zhang, Zhiguo Wang
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Abstract

IntroductionImmunotherapy benefits gastrointestinal tumor patients. But traditional biomarkers like TMB and MSI can't precisely identify beneficiaries. Phosphatidylinositol - 3,4,5 - triphosphate - dependent Rac exchange factor 2 (PREX2) plays a complex role in tumorigenesis.MethodsIn a retrospective study of 1764 patients (1385 colorectal, 379 gastric), NGS of 639 genes and PD - L1 staining were done.ResultsIn colorectal cancer, PREX2 mutations were associated with increased TMB, MSI, TMB-H, and MSI-H. Mechanistically, this is related to an increased number of tumor pathway mutations, higher PD - L1 expression, increased immune infiltration, and immune - related pathway enrichment. Cetuximab and Bortezomib sensitivity was higher in PREX2 - mutated colorectal cancer. In gastric cancer, there are no established immune associations with PREX2 mutations.ConclusionPREX2 mutations may serve as a novel predictive biomarker for immunotherapy in CRC, potentially enhancing antitumor immunity via microenvironment modulation, but lack predictive value in GC. These findings highlight PREX2's role in refining patient stratification for immune checkpoint inhibitors.

揭示PREX2突变作为结直肠癌免疫治疗反应的生物标志物的作用。
免疫治疗对胃肠道肿瘤患者有益。但是像TMB和MSI这样的传统生物标志物不能精确地识别受益人。磷脂酰肌醇- 3,4,5 -三磷酸依赖Rac交换因子2 (PREX2)在肿瘤发生中起复杂作用。方法回顾性分析1764例患者(结肠1385例,胃379例)639个基因的NGS和PD - L1染色。结果在结直肠癌中,PREX2突变与TMB、MSI、TMB- h和MSI- h升高相关。从机制上讲,这与肿瘤通路突变数量增加、PD - L1表达增加、免疫浸润增加和免疫相关通路富集有关。西妥昔单抗和硼替佐米在PREX2突变的结直肠癌中敏感性更高。在胃癌中,PREX2突变没有确定的免疫关联。结论prex2突变可能作为一种新的预测CRC免疫治疗的生物标志物,可能通过微环境调节增强抗肿瘤免疫,但在GC中缺乏预测价值。这些发现强调了PREX2在改善免疫检查点抑制剂患者分层中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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