Table_1_Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer.xlsx

Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC.

胃癌（GC）是一种具有高度分子与表型异质性的疾病，是全球范围内癌症相关死亡的主要病因之一。肿瘤免疫微环境（TIME）可影响胃癌患者的免疫治疗应答与预后。对胃癌肿瘤免疫微环境的探索以及分子亚型的特征解析，或可推动个体化治疗并助力临床决策制定。本研究基于免疫相关失调基因，通过无监督一致性聚类定义了两种胃癌分子亚型。随后研究发现，不同分子亚型的胃癌患者对免疫检查点抑制剂（ICBs）的敏感性存在显著差异。研究利用最小绝对收缩和选择算子（LASSO）-Cox回归分析构建了免疫相关预后特征（immune-related prognostic signature，以下简称IPRS）。通过三个独立外部队列以及IMvigor210队列，验证了IPRS的稳健性。利用胃癌样本的单细胞RNA测序（scRNA-seq）数据，解析了IPRS影响肿瘤免疫微环境的潜在机制。收集胃癌生物标本进行实时定量聚合酶链反应（RT-qPCR）实验，以进一步验证本研究结论。综上，本研究刻画了胃癌异常的肿瘤免疫微环境，并构建了一个与免疫治疗应答相关的可靠IPRS。本研究或可为胃癌患者的个体化治疗提供新的策略。