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基于SARS-CoV-2与肺腺癌相互作用基因的集成机器学习预测肺腺癌患者的预后

Integrated machine learning to predict the prognosis of lung adenocarcinoma patients based on SARS-COV-2 and lung adenocarcinoma crosstalk genes.

作者信息

Wu Yanan, Cui Yishuang, Zheng Xuan, Yao Xuemin, Sun Guogui

机构信息

School of Public Health, North China University of Science and Technology, Tangshan, China.

出版信息

Cancer Sci. 2025 Jan;116(1):95-111. doi: 10.1111/cas.16384. Epub 2024 Nov 3.

Abstract

Viruses are widely recognized to be intricately associated with both solid and hematological malignancies in humans. The primary goal of this research is to elucidate the interplay of genes between SARS-CoV-2 infection and lung adenocarcinoma (LUAD), with a preliminary investigation into their clinical significance and underlying molecular mechanisms. Transcriptome data for SARS-CoV-2 infection and LUAD were sourced from public databases. Differentially expressed genes (DEGs) associated with SARS-CoV-2 infection were identified and subsequently overlapped with TCGA-LUAD DEGs to discern the crosstalk genes (CGs). In addition, CGs pertaining to both diseases were further refined using LUAD TCGA and GEO datasets. Univariate Cox regression was conducted to identify genes associated with LUAD prognosis, and these genes were subsequently incorporated into the construction of a prognosis signature using 10 different machine learning algorithms. Additional investigations, including tumor mutation burden assessment, TME landscape, immunotherapy response assessment, as well as analysis of sensitivity to antitumor drugs, were also undertaken. We discovered the risk stratification based on the prognostic signature revealed that the low-risk group demonstrated superior clinical outcomes (p < 0.001). Gene set enrichment analysis results predominantly exhibited enrichment in pathways related to cell cycle. Our analyses also indicated that the low-risk group displayed elevated levels of infiltration by immunocytes (p < 0.001) and superior immunotherapy response (p < 0.001). In our study, we reveal a close association between CGs and the immune microenvironment of LUAD. This provides preliminary insight for further exploring the mechanism and interaction between the two diseases.

摘要

病毒与人类实体瘤和血液系统恶性肿瘤之间的复杂关联已得到广泛认可。本研究的主要目标是阐明严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染与肺腺癌(LUAD)之间的基因相互作用,并初步探究其临床意义和潜在分子机制。SARS-CoV-2感染和LUAD的转录组数据来源于公共数据库。识别出与SARS-CoV-2感染相关的差异表达基因(DEG),随后将其与TCGA-LUAD DEG进行重叠,以识别串扰基因(CG)。此外,使用LUAD TCGA和GEO数据集进一步细化与两种疾病相关的CG。进行单变量Cox回归以识别与LUAD预后相关的基因,随后使用10种不同的机器学习算法将这些基因纳入预后特征构建。还进行了其他研究,包括肿瘤突变负担评估、肿瘤微环境景观、免疫治疗反应评估以及对抗肿瘤药物敏感性分析。我们发现基于预后特征的风险分层显示低风险组具有更好的临床结局(p < 0.001)。基因集富集分析结果主要显示在与细胞周期相关的通路中富集。我们的分析还表明,低风险组免疫细胞浸润水平升高(p < 0.001)且免疫治疗反应更好(p < 0.001)。在我们的研究中,我们揭示了CG与LUAD免疫微环境之间的密切关联。这为进一步探索两种疾病之间的机制和相互作用提供了初步见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8847/11711064/f0cb2717d809/CAS-116-95-g002.jpg

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