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癌症相关成纤维细胞相关基因在肺腺癌中的预后价值。

Prognostic value of genes related to cancer-associated fibroblasts in lung adenocarcinoma.

机构信息

Department of Cardiothoracic Surgery, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, Fujian, China.

Department of Cardiothoracic Surgery, School of Clinical Medicine, Fujian Medical University, Ningde Municipal Hospital, Ningde, Fujian, China.

出版信息

Technol Health Care. 2023;31(6):2339-2354. doi: 10.3233/THC-230453.

Abstract

BACKGROUND

Although it has been established that cancer-associated fibroblasts (CAFs) facilitate tumor development, the relationship between CAFs and the prognosis of patients with lung adenocarcinoma (LUAD) has not been extensively explored.

OBJECTIVE

This study was formulated to investigate the prognostic value of CAF-related genes in LUAD.

METHODS

Differential analysis was carried out with TCGA-LUAD dataset as the training set. By overlapping differentially expressed genes (DEGs) with genes associated with CAF, CAF-related DEGs specific to LUAD were obtained. A prognostic risk model was constructed by Lasso and Cox regression analysis, and samples were grouped according to median risk score. The efficacy of the model was accessed through survival curve and receiver operating characteristic curve (ROC) analyses, with the validation set for verification. Risk score combined with clinical factors was utilized for Cox analysis to verify the independence of the model, and a nomogram was drawn. GSEA was performed on different risk groups. Immunologic infiltration and tumor mutational burden were assessed in different risk groups.

RESULTS

Eleven feature genes including DLGAP5, KCNE2, UPK2, NPAS2, ARHGAP11A, ANGPTL4, ANLN, DKK1, SMUG1, C16orf74, and ACAD8 were identified, based on which a prognostic model was constructed. Risk score could predict the prognosis of LUAD patients and could be an independent prognostic factor for LUAD patients. GSEA outcomes displayed significant enrichment of genes in the high-risk group in the P53 SIGNALING PATHWAY. In comparison to the low-risk group, the high-risk group exhibited a decreased degree of immune infiltration and an elevated level of tumor mutational burden.

CONCLUSION

An 11-gene model was constructed based on CAF-related genes to predict LUAD prognosis. This model represented an independent prognostic factor for LUAD.

摘要

背景

虽然已经证实癌症相关成纤维细胞(CAFs)有助于肿瘤的发展,但 CAFs 与肺腺癌(LUAD)患者预后之间的关系尚未得到广泛探讨。

目的

本研究旨在探讨 CAF 相关基因在 LUAD 中的预后价值。

方法

以 TCGA-LUAD 数据集作为训练集进行差异分析。通过将差异表达基因(DEGs)与 CAF 相关基因重叠,获得 LUAD 特异性 CAF 相关 DEGs。通过 Lasso 和 Cox 回归分析构建预后风险模型,并根据中位风险评分对样本进行分组。通过生存曲线和接收者操作特征曲线(ROC)分析评估模型的疗效,并通过验证集进行验证。风险评分结合临床因素进行 Cox 分析以验证模型的独立性,并绘制列线图。对不同风险组进行 GSEA 分析。评估不同风险组中的免疫浸润和肿瘤突变负担。

结果

基于 DLGAP5、KCNE2、UPK2、NPAS2、ARHGAP11A、ANGPTL4、ANLN、DKK1、SMUG1、C16orf74 和 ACAD8 等 11 个特征基因构建了预后模型。风险评分可预测 LUAD 患者的预后,并且可以作为 LUAD 患者的独立预后因素。GSEA 结果显示,高危组中与 P53 信号通路相关的基因显著富集。与低危组相比,高危组的免疫浸润程度降低,肿瘤突变负担增加。

结论

基于 CAF 相关基因构建了 11 基因模型来预测 LUAD 的预后。该模型是 LUAD 的独立预后因素。

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