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Hedgehog 信号相关基因组学特征可准确预测胃癌的进展和预后。

Hedgehog signaling-related genomics signature for the accurate progress and prognosis prediction in gastric cancer.

机构信息

Department of Gastrointestinal Surgery, Shaoxing Central Hospital, Shaoxing, China.

出版信息

Funct Integr Genomics. 2023 Feb 28;23(1):69. doi: 10.1007/s10142-023-00996-3.

Abstract

The Hedgehog pathway is thought to be closely associated with the progression of GC; however, a specific link between the Hedgehog pathway on the prognosis and immune infiltration of gastric cancer is still lacking. This study collected Hedgehog pathway-related genes. The Hedgehog pathway-related pattern were identified by consensus cluster analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the biological functions which were significantly altered between predefined Cluster1 and Cluster2 in consensus clustering. The risk model of gastric cancer based on Hedgehog signaling pathway was constructed by univariate and multivariate COX regression, and the nomogram was constructed. The results showed that there were significant differences in the expression of Hedgehog pathway-related genes between the two groups. In addition, the constructed risk model was significantly correlated with the clinical prognosis and immune cell infiltration level of patients with gastric cancer. The model effectively predicted the efficacy of chemotherapy in GC patients and the sensitivity of drug treatment between groups. We systematically revealed the mechanism of Hedgehog pathway in gastric cancer and selected biomarkers with biological significance from a new perspective, providing potential direction for the treatment of gastric cancer.

摘要

Hedgehog 通路被认为与 GC 的进展密切相关;然而,Hedgehog 通路与胃癌的预后和免疫浸润之间的确切联系仍不清楚。本研究收集了 Hedgehog 通路相关基因。通过共识聚类分析确定 Hedgehog 通路相关模式。基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)用于鉴定共识聚类中预先定义的 Cluster1 和 Cluster2 之间发生显著改变的生物学功能。通过单因素和多因素 COX 回归构建基于 Hedgehog 信号通路的胃癌风险模型,并构建列线图。结果表明,两组之间 Hedgehog 通路相关基因的表达存在显著差异。此外,构建的风险模型与胃癌患者的临床预后和免疫细胞浸润水平显著相关。该模型可有效预测 GC 患者化疗的疗效和组间药物治疗的敏感性。我们系统地揭示了 Hedgehog 通路在胃癌中的作用机制,并从新的角度选择了具有生物学意义的生物标志物,为胃癌的治疗提供了潜在的方向。

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