Construction of a prognostic model for lung adenocarcinoma based on necroptosis genes and its exploration of the potential for tumor immunotherapy.

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2025-05-30 Epub Date: 2025-05-26 DOI:10.21037/tcr-24-2165

Xiaoling Liu, Xin Li, Xiufen Shen, Run Ma, Zhuo Wang, Ying Hu

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引用次数: 0

Abstract

Background: Lung cancer ranks among the most prevalent malignancies globally, with lung adenocarcinoma (LUAD) being its most frequent histological subtype. Necroptosis is a newly defined mode of programmed cell death that is different from apoptosis and necrosis. However, the role of necroptosis in the occurrence and development of LUAD remains largely unexplored. This study aimed to construct a prognostic model of LUAD based on necroptosis-related genes (NRGs) and analyze the predictive value of this model on the prognosis of LUAD patients.

Methods: The dataset of LUAD patients was downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, and the NRGs were downloaded from inside GeneCards and Harmonizome databases. LUAD prognostic models were constructed by one-way Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis and multifactorial Cox regression analysis. Differential analyses of immune function as well as common tumor drugs were performed between high and low risk groups. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in LUAD. In this study, we leveraged bioinformatics to pinpoint genes implicated in necroptosis within LUAD.

Results: Two differentially expressed NRGs (DENRGs: KL, PLK1) were screened and used to construct the prognostic model and validate the RiskScore as an independent prognostic factor. Gene set variation analysis (GSVA) analysis showed that differentially expressed genes were mainly enriched in immune-related pathways. Additionally, we conducted experimental assays to validate the expression of these genes in LUAD cell lines. The GSVA analysis showed that differentially expressed genes were mainly enriched in immune-related pathways. Significant differences (P<0.05) were found between the high and low risk groups in terms of immune function and half-maximal inhibitory concentration (IC₅₀) values of five anticancer drugs (doxorubicin, lapatinib, paclitaxel, savolitinib and trametinib). We also identified a lncRNA SNHG14 /hsa-miR-101-3p/KL/PLK1 regulatory axis for LUAD.

Conclusions: The survival prognosis model of NRGs constructed in this study can predict the prognosis and immune microenvironment of LUAD patients.

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基于坏死下垂基因的肺腺癌预后模型的构建及其对肿瘤免疫治疗潜力的探索。

背景：肺癌是全球最常见的恶性肿瘤之一，肺腺癌（LUAD）是其最常见的组织学亚型。坏死上睑下垂是一种新定义的细胞程序性死亡模式，不同于细胞凋亡和坏死。然而，坏死性上睑下垂在LUAD发生和发展中的作用在很大程度上仍未被探索。本研究旨在构建基于坏死相关基因（necroposis - relevant genes, NRGs）的LUAD预后模型，并分析该模型对LUAD患者预后的预测价值。方法：从Cancer Genome Atlas （TCGA）数据库和Gene Expression Omnibus （GEO）数据库中下载LUAD患者数据集，从GeneCards和Harmonizome数据库中下载NRGs。采用单向Cox分析、最小绝对收缩和选择算子（LASSO）回归分析和多因素Cox回归分析构建LUAD预后模型。在高、低风险组之间进行免疫功能和常用肿瘤药物的差异分析。我们构建了一个ceRNA来探索LUAD中潜在的lncRNA-miRNA-mRNA调控轴。在这项研究中，我们利用生物信息学来确定LUAD中与坏死性下垂有关的基因。结果：筛选了两种差异表达的NRGs (DENRGs: KL, PLK1)，用于构建预后模型并验证RiskScore作为独立预后因素。基因集变异分析（GSVA）显示，差异表达基因主要富集于免疫相关通路。此外，我们进行了实验分析，以验证这些基因在LUAD细胞系中的表达。GSVA分析显示，差异表达基因主要富集于免疫相关通路。5种抗癌药（阿霉素、拉帕替尼、紫杉醇、沙伐替尼、曲美替尼）的P50值有显著差异。我们还发现了LUAD的lncRNA SNHG14 /hsa-miR-101-3p/KL/PLK1调控轴。结论：本研究构建的NRGs生存预后模型可以预测LUAD患者的预后和免疫微环境。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.