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一种用于肺腺癌肿瘤免疫微环境评估和预后预测的新型线粒体相关基因特征

英文原题:A Novel Mitochondrial-Related Gene Signature for the Tumor Immune Microenvironment Evaluation and Prognosis Prediction in Lung Adenocarcinoma.

查看英文原题

A Novel Mitochondrial-Related Gene Signature for the Tumor Immune Microenvironment Evaluation and Prognosis Prediction in Lung Adenocarcinoma.

PubMed 2022/05/25(内容时间) J Immunol Res Q3 · IF 3.2(JCR 2025)

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中文摘要

肺腺癌(LUAD)仍是最常见的致死性疾病,预后较差。越来越多研究分别报告了线粒体相关基因(MTRG)与多种肿瘤临床结局的关联。

本研究旨在基于 MTRG 建立一种新的预后模型。研究者从 TCGA-LUAD 和 GSE31210 队列鉴定差异表达的 MTRG,并采用单变量 Cox 回归筛选与 LUAD 预后相关的差异表达 MTRG;随后使用 LASSO Cox 回归分析建立预后特征,并使用 ESTIMATE 估算免疫细胞类型比例。

本研究在 TCGA-LUAD 和 GSE31210 队列中共鉴定出 44 个重叠的差异表达 MTRG,其中 9 个基因与 LUAD 预后相关。当惩罚参数 λ 取最小值时,有 6 个基因符合构建特征的条件,包括 SERPINB5、CCNB1、FGR、MAOB、SH3BP5 和 CYP24A1。生存分析显示,高风险组患者预后显著差于低风险组。Cox 回归分析表明,风险评分是 LUAD 预后的独立预测因子。ESTIMATE 评分结果显示,低风险组免疫细胞浸润程度高于高风险组,例如 TIL、Treg 和 B 细胞。

此外,低风险组的肿瘤突变负荷(TMB)和癌症干细胞浸润均高于高风险组。总之,我们开发了一种新的 MTRG 特征,可作为负向独立预后因素。未来,个体化治疗和医疗决策或可从该预测模型中获益。

展开英文摘要原文

Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. More and more studies have reported that mitochondrial-related genes (MTRGs) were associated with the clinical outcomes of multiple tumors solely. In this study, we aimed to develop a novel prognostic model based on MTRGs. Differentially expressed MTRGs were identified from TCGA-LUAD and GSE31210 cohorts. Univariate Cox regression analysis was utilized to screen differentially expressed MTRGs that were related to prognosis of LUAD. Then, LASSO Cox regression analysis was used to develop a prognostic signature. ESTIMATE was used for estimating the fractions of immune cell types. In this study, we identified 44 overlapping differentially expressed MTRGs in TCGA-LUAD and GSE31210 cohorts.

Among 44 overlapping differentially expressed MTRGs, nine genes were associated with prognosis of LUAD. When the penalty parameter lambda was the minimum, there were six genes meeting the conditions of constructing the signature, including SERPINB5, CCNB1, FGR MAOB, SH3BP5, and CYP24A1.

The survival analysis suggested that prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. Cox regression analyses showed that the risk score was an independent predictor of LUAD prognosis. As with the results of ESTIMATE score, the degree of immune cell infiltration in the low-risk group was higher than that in the high-risk group, such as TIL, Treg, and B cells.

In addition, TMB and cancer stem cell infiltration were higher in the low-risk group than the high-risk group.

In conclusion, we developed a novel MTRG signature acting as a negative independent prognostic factor. In the future, individualized treatments and medical decision-making may benefit from using the predicted model.

论文信息

作者
Li YP、Liu GX、Wu ZL、Tu PH、Wei G、Yuan M、Zhong MH、Deng KL
单位
Department of Respiratory and Critical Care Medicine, The Center Hospital of Xiaogan, Xiaogan, Hubei, China.China
期刊
Journal of immunology research2022
原文标识
PubMed 35664356 · DOI 10.1155/2022/5366185