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一种新型的与 mTOR 相关的基因标志物,可用于预测肺腺癌的预后和评估肿瘤免疫微环境。

A novel mTOR-associated gene signature for predicting prognosis and evaluating tumor immune microenvironment in lung adenocarcinoma.

机构信息

Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China.

Department of General Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China.

出版信息

Comput Biol Med. 2022 Jun;145:105394. doi: 10.1016/j.compbiomed.2022.105394. Epub 2022 Mar 18.

Abstract

BACKGROUND

The mechanistic target of rapamycin (mTOR) was proven to have great impact on apoptosis, cell proliferation, autophagy, and many other fundamental cellular processes; moreover, it closely correlates with tumor occurrence and development. However, few studies have constructed signatures based on mTOR-associated genes to assess multiple indicators of prognosis in lung adenocarcinoma (LUAD) patients.

METHODS

mTOR-associated gene sets, whole mRNA expression matrices, and clinical information of LUAD patients in training and validation cohorts were obtained from multiple public databases. Multiple methods were used to screen candidate genes, construct signatures, validate internally and externally, and conduct further studies: differentially expressed gene analysis, LASSO Cox regression analysis, Cox regression analysis, risk factor analysis, nomogram analysis, functional enrichment analysis, analyses in tumor immune microenvironment, and therapy.

RESULTS

A prognostic signature containing 8 genes (LDHA, SLA, WNT7A, PLK1, CCT6A, BTG2, TXNRD1, and DDIT4) was constructed. It performed well in both internal and external validation. Subsequent analysis found that the prognostic signature was of great significance in evaluating the tumor immune microenvironment and could guide the treatment of patients with LUAD to a certain extent.

CONCLUSION

The constructed mTOR-associated gene signature accurately predicted the prognostic pattern of patients with LUAD and is expected to be extremely useful in guiding LUAD therapy.

摘要

背景

雷帕霉素靶蛋白(mTOR)的作用机制已被证明对细胞凋亡、细胞增殖、自噬和许多其他基本细胞过程有重大影响;此外,它与肿瘤的发生和发展密切相关。然而,很少有研究基于 mTOR 相关基因构建签名来评估肺腺癌(LUAD)患者的多种预后指标。

方法

从多个公共数据库中获取 mTOR 相关基因集、全 mRNA 表达矩阵和 LUAD 患者的临床信息,用于训练和验证队列。使用多种方法筛选候选基因,构建签名,内部和外部验证,并进行进一步研究:差异表达基因分析、LASSO Cox 回归分析、Cox 回归分析、风险因素分析、列线图分析、功能富集分析、肿瘤免疫微环境分析和治疗分析。

结果

构建了一个包含 8 个基因(LDHA、SLA、WNT7A、PLK1、CCT6A、BTG2、TXNRD1 和 DDIT4)的预后签名。该签名在内部和外部验证中表现良好。随后的分析发现,该预后签名在评估肿瘤免疫微环境方面具有重要意义,并在一定程度上可以指导 LUAD 患者的治疗。

结论

构建的 mTOR 相关基因签名能够准确预测 LUAD 患者的预后模式,有望在指导 LUAD 治疗方面具有重要价值。

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