失巢凋亡相关基因与胰腺癌患者的预后相关。
Anoikis-related genes linked with patient outcome in pancreatic cancer.
发表日期:2024 Aug 16
作者:
Lizhi Lin, Jing Deng, Jiaye Yu, Monika Bauden, Roland Andersson, Xian Shen, Daniel Ansari, Xiangyang Xue
来源:
Cellular & Molecular Immunology
摘要:
失巢凋亡是细胞从细胞外基质脱离时发生的程序性细胞死亡。癌细胞需要逃避失巢凋亡才能转移到远处。然而,胰腺癌中失巢凋亡相关基因(ARG)的分子特征和预后价值仍不清楚。在这项研究中,我们利用 TCGA 和 GSE102238 数据库的转录组数据来识别 64 个与预后显着相关的 ARG。我们使用“ConsensusClusterPlus”R 包将患者分为高风险和低风险预后亚组。 KEGG和GSEA分析显示,预后不良的簇在ECM受体相互作用通路、TP53信号通路和半乳糖代谢通路上富集,并且细胞周期通路上调。使用 LASSO 回归构建了由 7 个 ARG(SERPINE1、EGF、E2F1、MSLN、RAB27B、ETV7、MST1)组成的预后模型,并使用 Cox 回归与临床病理参数相结合,创建了预后列线图,显示出较高的预后效用。在候选生物标志物中,我们将 ETV7 报告为胰腺癌的一种新型独立预后标志物。 ETV7在KRAS和TP53共现突变的TCGA患者中高表达,表明它可能受到胰腺癌的两个主要驱动基因的调控。因此,靶向 ETV7 可能成为未来治疗研究的潜在焦点。版权所有 © 2024。由 Elsevier B.V. 出版。
Anoikis is programmed cell death occurring upon cell detachment from the extracellular matrix. Cancer cells need to evade anoikis to be able to metastasize to distant sites. However, the molecular features and prognostic value of anoikis-related genes (ARGs) in pancreatic cancer remain unclear. In this study, we utilized transcriptome data from the TCGA and GSE102238 databases to identify 64 ARGs significantly associated with prognosis. We used the "ConsensusClusterPlus" R package to stratify patients into high and low-risk prognostic subgroups. The KEGG and GSEA analyses revealed that the clusters with poor prognosis were enriched for the ECM receptor interaction pathway, the TP53 signaling pathway, and the galactose metabolism pathway, and that the cell cycle pathway was upregulated. A prognostic model consisting of seven ARGs (SERPINE1, EGF, E2F1, MSLN, RAB27B, ETV7, MST1) was constructed using LASSO regression and when combined with clinicopathological parameters using Cox regression, a prognostic Nomogram was created, which demonstrated high prognostic utility. Among the biomarker candidates, we report ETV7 as a novel, independent prognostic marker in pancreatic cancer. ETV7 was highly expressed in KRAS and TP53 co-occurrent mutant TCGA patients, indicating that it may be regulated by the two major driver genes of pancreatic cancer. Therefore, targeting ETV7 could be a potential focus for future therapeutic studies.Copyright © 2024. Published by Elsevier B.V.