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内质网应激相关基因在非小细胞肺癌中的临床意义及CAV1单核苷酸多态性分析

The clinical significance of endoplasmic reticulum stress related genes in non-small cell lung cancer and analysis of single nucleotide polymorphism for CAV1.

作者信息

Li Shuang, Chen Junting, Zhou Baosen

机构信息

Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Hospital of China Medical University, Shenyang, China.

出版信息

Front Mol Biosci. 2024 Aug 6;11:1414164. doi: 10.3389/fmolb.2024.1414164. eCollection 2024.

Abstract

In recent years, protein homeostasis imbalance caused by endoplasmic reticulum stress has become a major hallmark of cancer. Studies have shown that endoplasmic reticulum stress is closely related to the occurrence, development, and drug resistance of non-small cell lung cancer, however, the role of various endoplasmic reticulum stress-related genes in non-small cell lung cancer is still unclear. In this study, we established an endoplasmic reticulum stress scores based on the Cancer Genome Atlas for non-small cell lung cancer to reflect patient features and predict prognosis. Survival analysis showed significant differences in overall survival among non-small cell lung cancer patients with different endoplasmic reticulum stress scores. In addition, endoplasmic reticulum stress scores was significantly correlated with the clinical features of non-small cell lung cancer patients, and can be served as an independent prognostic indicator. A nomogram based on endoplasmic reticulum stress scores indicated a certain clinical net benefit, while ssGSEA analysis demonstrated that there was a certain immunosuppressive microenvironment in high endoplasmic reticulum stress scores. Gene Set Enrichment Analysis showed that scores was associated with cancer pathways and metabolism. Finally, weighted gene co-expression network analysis displayed that CAV1 was closely related to the occurrence of non-small cell lung cancer. Therefore, in order to further analyze the role of this gene, Chinese non-smoking females were selected as the research subjects to investigate the relationship between CAV1 rs3779514 and susceptibility and prognosis of non-small cell lung cancer. The results showed that the mutation of rs3779514 significantly reduced the risk of non-small cell lung cancer in Chinese non-smoking females, but no prognostic effect was found. In summary, we proposed an endoplasmic reticulum stress scores, which was an independent prognostic factor and indicated immune characteristics in the microenvironment of non-small cell lung cancer. We also validated the relationship between single nucleotide polymorphism locus of core genes and susceptibility to non-small cell lung cancer.

摘要

近年来,内质网应激导致的蛋白质稳态失衡已成为癌症的一个主要标志。研究表明,内质网应激与非小细胞肺癌的发生、发展及耐药性密切相关,然而,各种内质网应激相关基因在非小细胞肺癌中的作用仍不清楚。在本研究中,我们基于癌症基因组图谱建立了非小细胞肺癌的内质网应激评分,以反映患者特征并预测预后。生存分析显示,不同内质网应激评分的非小细胞肺癌患者总生存存在显著差异。此外,内质网应激评分与非小细胞肺癌患者的临床特征显著相关,可作为独立的预后指标。基于内质网应激评分的列线图显示出一定的临床净效益,而单样本基因集富集分析表明,内质网应激评分高时存在一定的免疫抑制微环境。基因集富集分析表明,评分与癌症通路和代谢相关。最后,加权基因共表达网络分析显示,CAV1与非小细胞肺癌的发生密切相关。因此,为进一步分析该基因的作用,选取中国非吸烟女性作为研究对象,探讨CAV1 rs3779514与非小细胞肺癌易感性及预后的关系。结果显示,rs3779514突变显著降低了中国非吸烟女性患非小细胞肺癌的风险,但未发现其对预后有影响。综上所述,我们提出了一种内质网应激评分,它是一个独立的预后因素,表明了非小细胞肺癌微环境中的免疫特征。我们还验证了核心基因单核苷酸多态性位点与非小细胞肺癌易感性的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b14/11334084/a582323f9ade/fmolb-11-1414164-g001.jpg

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