胃癌干细胞（GCSC）与胃癌的难治性特征密切相关，包括耐药性、复发和转移。术后接受多模式治疗的晚期胃癌患者的预后仍然令人沮丧。 GCSC 有望成为 GC 患者的治疗靶点。我们从StemChecker数据库中获得了26组干细胞相关基因。采用共识聚类算法来辨别三种不同的干性子类型。比较了这些亚型的预后结果、肿瘤微环境 (TME) 的组成部分以及对治疗的反应。随后，使用加权基因相关网络分析 (WGCNA) 以及 Cox 回归和随机生存森林分析制定了干性风险模型。 C2 亚型主要表现出阴性预后 CSC 基因集的富集，并表现出免疫抑制性 TME。这种特定的亚型对免疫疗法的反应性极小，并且对药物的敏感性降低。四个关键基因被整合到干性模型的构建中。干性风险评分较高的胃癌患者预后较差，TME 中免疫抑制成分较多，治疗反应率较低。子集分析表明，只有低干风险亚型才能从基于 5-氟尿嘧啶的辅助化疗中获益。该模型在免疫治疗预测方面的有效性在 PRJEB25780 队列中得到了进一步验证。我们的研究将胃癌患者分为三种干细胞亚型，每种亚型都表现出不同的预后、TME 浸润的组成部分，以及对标准化疗或靶向治疗的不同敏感性或耐药性。我们认为干性风险模型可能有助于制定有根据的治疗建议和预后评估。版权所有 © 2023。由 Elsevier Inc. 出版。

Gastric cancer stem cells (GCSCs) are strongly associated with the refractory characteristics of gastric cancer, including drug resistance, recurrence, and metastasis. The prognosis for advanced gastric cancer patients treated with multimodal therapy after surgery remains discouraging. GCSCs hold promise as therapeutic targets for GC patients. We obtained 26 sets of stem cell-related genes from the StemChecker database. The Consensus clustering algorithm was employed to discern three distinct stemness subtypes. Prognostic outcomes, components of the tumor microenvironment (TME), and responses to therapies were compared among these subtypes. Following this, a stemness-risk model was formulated using weighted gene correlation network analysis (WGCNA), alongside Cox regression and random survival forest analyses. The C2 subtype predominantly showed enrichment in negative prognostic CSC gene sets and demonstrated an immunosuppressive TME. This specific subtype exhibited minimal responsiveness to immunotherapies and demonstrated reduced sensitivity to drugs. Four pivotal genes were integrated into the construction of the stemness model. Gastric cancer patients with higher stemness-risk scores demonstrated poorer prognoses, a greater presence of immunosuppressive components in TME, and lower rates of treatment response. Subset analysis indicated that only the low-stemness risk subtype derives benefit from 5-fluorouracil-based adjuvant chemotherapy. The model's effectiveness in immunotherapeutic prediction was further validated in the PRJEB25780 cohort. Our study categorized gastric cancer patients into three stemness subtypes, each demonstrating distinct prognoses, components of TME infiltration, and varying sensitivity or resistance to standard chemotherapy or targeted therapy. We propose that the stemness risk model may help the development of well-grounded treatment recommendations and prognostic assessments.Copyright © 2023. Published by Elsevier Inc.