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通过加权基因共表达网络分析(WGCNA)结合套索(LASSO)算法构建胃腺癌患者的预后模型。

Construction of a prognostic model via WGCNA combined with the LASSO algorithm for stomach adenocarcinoma patients.

作者信息

Huang Zi-Duo, Ran Wen-Hua, Wang Guo-Zhu

机构信息

Department of General Surgery, Qianjiang Central Hospital of Chongqing, Chongqing, China.

Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Front Genet. 2024 Aug 7;15:1418818. doi: 10.3389/fgene.2024.1418818. eCollection 2024.

Abstract

OBJECTIVE

This study aimed to identify prognostic signatures to predict the prognosis of patients with stomach adenocarcinoma (STAD), which is necessary to improve poor prognosis and offer possible treatment strategies for STAD patients.

METHODS

The overlapping genes between the key model genes that were screened by the weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) whose expression was different with significance between normal and tumor tissues were extracted to serve as co-expression genes. Then, enrichment analysis was performed on these genes. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression was performed to screen the hub genes among overlapping genes. Finally, we constructed a model to explore the influence of polygenic risk scores on the survival probability of patients with STAD, and interaction effect and mediating analyses were also performed.

RESULTS

DEGs included 2,899 upregulated genes and 2,896 downregulated genes. After crossing the DEGs and light-yellow module genes that were obtained by WGCNA, a total of 39 overlapping genes were extracted. The gene enrichment analysis revealed that these genes were enriched in the prion diseases, biosynthesis of unsaturated fatty acids, RNA metabolic process, hydrolase activity, etc. PIP5K1P1, PTTG3P, and SNORD15B were determined by LASSO-Cox. The prognostic prediction of the three-gene model was established. The Cox regression analysis showed that the comprehensive risk score for three genes was an independent prognosis factor.

CONCLUSION

PIP5K1P1, PTTG3P, and SNORD15B are related to the prognosis and overall survival of patients. The three-gene risk model constructed has independent prognosis predictive ability for STAD.

摘要

目的

本研究旨在识别预后特征以预测胃腺癌(STAD)患者的预后,这对于改善不良预后以及为STAD患者提供可能的治疗策略是必要的。

方法

提取通过加权基因共表达网络分析(WGCNA)筛选出的关键模型基因与正常组织和肿瘤组织之间表达有显著差异的差异表达基因(DEG)之间的重叠基因作为共表达基因。然后,对这些基因进行富集分析。此外,进行最小绝对收缩和选择算子(LASSO)回归以筛选重叠基因中的核心基因。最后,我们构建了一个模型来探索多基因风险评分对STAD患者生存概率的影响,并进行了交互作用分析和中介分析。

结果

DEG包括2899个上调基因和2896个下调基因。将DEG与通过WGCNA获得的浅黄模块基因交叉后,共提取出39个重叠基因。基因富集分析表明这些基因富集于朊病毒病、不饱和脂肪酸的生物合成、RNA代谢过程、水解酶活性等。通过LASSO-Cox确定了PIP5K1P1、PTTG3P和SNORD15B。建立了三基因模型的预后预测方法。Cox回归分析表明,三个基因的综合风险评分是一个独立的预后因素。

结论

PIP5K1P1、PTTG3P和SNORD15B与患者的预后和总生存期相关。构建的三基因风险模型对STAD具有独立的预后预测能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/052a/11335515/0e66a8e25618/fgene-15-1418818-g001.jpg

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