Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China.
OrigiMed Inc., Shanghai 201112, China.
Aging (Albany NY). 2020 Dec 3;13(1):714-734. doi: 10.18632/aging.202179.
RhoA is a member of the RHO family GTPases and is associated with essential functions in gastric cancer. In this study, we identified a gastric cancer biomarker, termed the "regulation of RhoA activity panel" (RRAP). Patients with gastric cancer from The Cancer Genome Atlas database were divided into training (N=160) and validation (N=155) cohorts. A cohort of 109 Chinese gastric cancer patients was utilized as an independent validation. Patients with mutated RRAP showed significantly better overall survival than patients with wild type RRAP. We also analyzed the association between RRAP and the migration capacity, immune-related signatures, and the tumor microenvironment. RRAP-mutant tumors had a significantly lower degree of lymph node metastasis and lower activities of migration-related pathways. These tumors also showed significantly increased immune cell infiltration and cytotoxic activity. Furthermore, two independent patient cohorts who received immune checkpoint blockade therapy were assessed for RRAP mutant status. As expected, for both immunotherapy cohorts, higher response rates to immune checkpoint blockade therapy were observed in patients with RRAP-mutant tumors than in patients with wild type RRAP tumors. Overall, this study indicates that the RRAP gene set is a potential biomarker for gastric cancer prognosis and therapeutic selection.
RhoA 是 RHO 家族 GTPases 的成员，与胃癌的基本功能有关。在这项研究中，我们鉴定了一种胃癌生物标志物，称为“RhoA 活性调节面板”（RRAP）。来自癌症基因组图谱数据库的胃癌患者被分为训练（N=160）和验证（N=155）队列。109 例中国胃癌患者的队列被用作独立验证。具有突变 RRAP 的患者的总生存率明显优于具有野生型 RRAP 的患者。我们还分析了 RRAP 与迁移能力、免疫相关特征和肿瘤微环境之间的关系。RRAP 突变型肿瘤的淋巴结转移程度明显较低，迁移相关途径的活性也较低。这些肿瘤还显示出明显增加的免疫细胞浸润和细胞毒性活性。此外，还评估了接受免疫检查点阻断治疗的两个独立患者队列的 RRAP 突变状态。正如预期的那样，对于两个免疫治疗队列，RRAP 突变型肿瘤患者对免疫检查点阻断治疗的反应率均高于野生型 RRAP 肿瘤患者。总的来说，这项研究表明，RRAP 基因集是胃癌预后和治疗选择的潜在生物标志物。
