Geng Haigang, Dong Zhongyi, Zhang Linmeng, Yang Chen, Li Tingting, Lin Yuxuan, Ke Shouyu, Xia Xiang, Zhang Zizhen, Zhao Gang, Zhu Chunchao
Department of Gastrointestinal Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China.
Cancers (Basel). 2022 Jul 4;14(13):3276. doi: 10.3390/cancers14133276.
Helicobacter pylori (HP) infection is the greatest risk factor for gastric cancer (GC). Increasing evidence has clarified that tumor immune microenvironment (TIME) is closely related to the prognosis and therapeutic efficacy of HP-positive (HP+) GC patients. In this study, we aimed to construct a novel immune-related signature for predicting the prognosis and immunotherapy efficacy of HP+ GC patients. A total of 153 HP+ GC from three different cohorts were included in this study. An Immune-Related prognostic Signature for HP+ GC patients (IRSHG) was established using Univariate Cox regression, the LASSO algorithm, and Multivariate Cox regression. Univariate and Multivariate analyses proved IRSHG was an independent prognostic predictor for HP+ GC patients, and an IRSHG-integrated nomogram was established to quantitatively assessthe prognostic risk. The low-IRSHG group exhibited higher copy number load and distinct mutation profiles compared with the high-IRSHG group. In addition, the difference of hallmark pathways and immune cells infiltration between the two groups was investigated. Notably, tumor immune dysfunction and exclusion (TIDE) analysis indicated that the low-IRSHG group had a higher sensitivity to anti-PD-1 immunotherapy, which was validated by an external pabolizumab treatment cohort. Moreover, 98 chemotherapeutic drugs and corresponding potential biomarkers were identified for two groups, and several drugs with potential ability to reverse IRSHG score were identified using CMap analysis. Collectively, IRSHG may serve as a promising biomarker for survival outcome as well as immunotherapy efficacy. Furthermore, it can also help to prioritize potential therapeutics for HP+ GC patients, providing new insight for the personalized treatment of HP-infected GC.
幽门螺杆菌（HP）感染是胃癌（GC）的最大风险因素。越来越多的证据表明，肿瘤免疫微环境（TIME）与HP阳性（HP+）GC患者的预后和治疗效果密切相关。在本研究中，我们旨在构建一种新的免疫相关特征，用于预测HP+ GC患者的预后和免疫治疗效果。本研究共纳入了来自三个不同队列的153例HP+ GC患者。使用单变量Cox回归、LASSO算法和多变量Cox回归建立了HP+ GC患者的免疫相关预后特征（IRSHG）。单变量和多变量分析证明IRSHG是HP+ GC患者的独立预后预测指标，并建立了一个整合IRSHG的列线图来定量评估预后风险。与高IRSHG组相比，低IRSHG组表现出更高的拷贝数负荷和不同的突变谱。此外，还研究了两组之间标志性通路和免疫细胞浸润的差异。值得注意的是，肿瘤免疫功能障碍和排除（TIDE）分析表明，低IRSHG组对抗PD-1免疫治疗具有更高的敏感性，这在一个外部帕博利珠单抗治疗队列中得到了验证。此外，还为两组鉴定了98种化疗药物和相应的潜在生物标志物，并使用CMap分析鉴定了几种具有逆转IRSHG评分潜在能力的药物。总的来说，IRSHG可能是一种有前景的生物标志物，可用于预测生存结果和免疫治疗效果。此外，它还可以帮助为HP+ GC患者确定潜在治疗方法的优先级，为HP感染的GC的个性化治疗提供新的见解。
