Identifying key transcription factors and immune infiltration in non-small-cell lung cancer using weighted correlation network and Cox regression analyses

Frontiers in Oncology

Oncology

Hefen Yu¹  Xu Teng¹  Wei Huang¹  Yong Wang²  Hao Qin³  Jingyao Zhang³  Jun Zou³  Min Zhang³  Yinuo Wang³  Baowen Yuan³  Yan Wang³  Yunkai Yang³ 

[1] Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China;Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;

关键词: Transcription Factors;    WGCNA;    Cox regression analysis;    LASSO analysis;    Immune infiltration;    NSCLC;   

DOI  :  10.3389/fonc.2023.1112020

 received in 2022-11-30, accepted in 2023-04-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionLung cancer is one of the most common cancers and a significant cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Therefore, it is crucial to identify effective diagnostic and therapeutic methods. In addition, transcription factors are essential for eukaryotic cells to regulate their gene expression, and aberrant expression transcription factors are an important step in the process of oncogenesis in NSCLC. MethodsDifferentially expressed transcription factors between NSCLC and normal tissues by analyzing mRNA profiling from The Cancer Genome Atlas (TCGA) database program were identified. Weighted correlation network analysis (WGCNA) and line plot of least absolute shrinkage and selection operator (LASSO) were performed to find prognosis-related transcription factors. The cellular functions of transcription factors were performed by 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay, cell invasion assay in lung cancer cells.ResultsWe identified 725 differentially expressed transcription factors between NSCLC and normal tissues. Three highly related modules for survival were discovered, and transcription factors highly associated with survival were obtained by using WGCNA. Then line plot of LASSO was applied to screen transcription factors related to prognosis and build a prognostic model. Consequently, SETDB2, SNAI3, SCML4, and ZNF540 were identified as prognosis-related transcription factors and validated in multiple databases. The low expression of these hub genes in NSCLC was associated with poor prognosis. The deletions of both SETDB2 and SNAI3 were found to promote proliferation, invasion, and stemness in lung cancer cells. Furthermore, there were significant differences in the proportions of 22 immune cells between the high- and low-score groups. DiscussionTherefore, our study identified the transcription factors involved in regulating NSCLC, and we constructed a panel for the prediction of prognosis and immune infiltration to inform the clinical application of transcription factor analysis in the prevention and treatment of NSCLC.

【 授权许可】

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Copyright © 2023 Zhang, Wang, Yuan, Qin, Wang, Yu, Teng, Yang, Zou, Zhang, Huang and Wang