Identification of "regulation of RhoA activity panel" as a prognostic and predictive biomarker for gastric cancer.
Identification of "regulation of RhoA activity panel" as a prognostic and predictive biomarker for gastric cancer.
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鉴定“RhoA 活性组的调节”作为胃癌的预后和预测生物标志物
DOI：
10.18632/aging.202179
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发表时间：
2020-12-03
期刊：
影响因子：
--
通讯作者：
Shen L
中科院分区：
文献类型：
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作者：
Huang W;Zhao S;Zhang C;Li Z;Ge S;Lian B;Feng H;Wang K;Xu R;Ji J;Gao J;Shi W;Shen L
RhoA是RHO家族GTPases的成员，与胃癌的基本功能相关。在这项研究中，我们确定了一种胃癌生物标志物，称为“RhoA活性调控面板”（RRAP）。将来自癌症基因组图谱数据库的胃癌患者分为训练（N=160）和验证（N=155）队列。109名中国胃癌患者的队列被用作独立验证。与野生型RRAP患者相比，突变型RRAP患者的总体生存率明显更好。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联。RRAP突变型肿瘤的淋巴结转移程度明显较低，迁移相关通路的活性也较低。这些肿瘤还显示出显著增加的免疫细胞浸润和细胞毒活性。此外，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，在RRAP突变型肿瘤患者中观察到对免疫检查点阻断治疗的应答率高于野生型RRAP肿瘤患者。总之，本研究表明RRAP基因集是胃癌预后和治疗选择的潜在生物标志物。
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.