Hedgehog信号通路是一种高度保守的途径，用于调节细胞生长和增殖，在胃腺癌（STAD）和其他癌症类型中发挥着重要作用。然而，先前的研究主要以mRNA或体外细胞培养为基础。结合单细胞RNA测序（scRNA-seq）数据进行整合将更加有说服力，因为它是一种更精确的基因组研究方法。本研究调查了Hedgehog信号通路的表达谱、遗传变异和活性在STAD的scRNA-seq和RNA-seq数据集中。通过cell-chat算法确定了癌细胞与成纤维细胞之间的通信，并构建了Hedgehog相关基因签名以预测STAD的生存情况。根据签名的中位数，将患者分为高风险组和低风险组。进一步分析了两组之间的生存结果、肿瘤免疫微环境（TIME）和药物敏感性的差异，旨在指导STAD患者化疗和免疫治疗的使用。Hedgehog信号通路在STAD中超活化。GAS1、GLI1和SCEBU2被认为是STAD预后签名中的枢纽基因，并被视为引发不良生存结果的强有力风险因素。高风险组患者表现出耗竭的TIME模式，并对分子靶向药物的敏感性较低。本研究描述了Hedgehog途径对STAD的生存结果、TIME和药物敏感性的影响，并为STAD的治疗提供了新的见解。© 2023. 作者，独家许可给Springer-Verlag GmbH Germany，Springer Nature的一部分。

The Hedgehog signaling is a highly conserved pathway to regulate cell growth and proliferation, and plays an essential role in stomach adenocarcinoma (STAD) and other cancer types. However, previous studies were primarily conducted in terms of mRNA or vitro cell culture. It would be more convincing to integrate single-cell RNA sequencing (scRNA-seq) data because it is a more precise approach for genomic research. The expression profile, genetic alteration, and activity of the Hedgehog signaling pathway were investigated in both scRNA-seq and RNA-seq datasets of STAD. Communications between cancer cells and fibroblasts were determined by the cell-chat algorithm, and the Hedgehog-related gene signature was constructed to predict the survival of STAD. Patients were categorized into high- and low-risk groups according to the median of the signature. Further analysis explored the difference in survival outcome, tumor immune microenvironment (TIME), and drug sensitivity between the two groups, aiming to guide the use of chemotherapy and immunotherapy in STAD patients. Hedgehog signal pathway was over-activated in STAD. GAS1, GLI1, and SCEBU2 were recognized as hub genes in the prognostic signature of STAD, and served as robust risk factors to induce a poor survival outcome. Patients in the high-risk group demonstrated an exhausted TIME pattern, with rather low sensitivity toward molecular-targeted drugs. This study depicted the influence of the Hedgehog pathway on the survival outcome, TIME, and drug sensitivity of STAD, and provides novel insights for the treatment of STAD.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.