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套索回归和生物信息学分析在妇科癌症预后关键基因鉴定中的应用

LASSO and Bioinformatics Analysis in the Identification of Key Genes for Prognostic Genes of Gynecologic Cancer.

作者信息

Yu Shao-Hua, Cai Jia-Hua, Chen De-Lun, Liao Szu-Han, Lin Yi-Zhen, Chung Yu-Ting, Tsai Jeffrey J P, Wang Charles C N

机构信息

School of Medicine, College of Medicine, China Medical University, Taichung 404333, Taiwan.

Department of Emergency Medicine, China Medical University Hospital, Taichung 404333, Taiwan.

出版信息

J Pers Med. 2021 Nov 11;11(11):1177. doi: 10.3390/jpm11111177.

Abstract

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients ( < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium-calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment.

摘要

本研究的目的是识别用于妇科癌症早期诊断的潜在生物标志物,以提高生存率。宫颈癌(CC)和子宫内膜癌(EC)是全球女性中最常见的妇科恶性肿瘤。由于宫颈癌和子宫内膜癌的潜在分子机制仍不清楚,因此需要进行全面系统的生物信息学分析。在我们的研究中,利用从基因表达综合数据库(GEO)下载的GSE9750、GES7803、GES63514、GES17025、GES115810和GES36389的基因表达谱,分析癌症组织与正常组织之间的差异基因表达。共鉴定出78个CC和EC共有的差异表达基因(DEG),用于进行功能富集分析,包括基因本体论和通路分析。对78个DEG的KEGG通路分析表明,药物代谢、信号转导以及肿瘤发生和发展等三种主要类型的通路参与了妇科癌症的发生机制。此外,使用最小绝对收缩和选择算子(LASSO)回归及10倍交叉验证确认了20个诊断特征。最后,我们使用GEPIA2在线工具验证LASSO回归模型选择的20个基因的表达。其中,与正常组织相比,肿瘤组织中PAMR1和SLC24A3的表达显著下调,并且在CC和EC患者的生存率之间具有统计学意义(<0.05)。这两个基因具有以下功能:(1.)PAMR1是一种肿瘤抑制基因,许多研究证明该基因的过表达显著抑制细胞生长,尤其是在乳腺癌和多囊卵巢综合征中;(2.)SLC24A3是细胞的钠钙调节剂,SLC24A3水平高与预后不良相关。在我们的研究中,基因特征可用于预测CC和EC的预后,这可为未来的诊断和治疗提供新的临床证据,作为一种潜在的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95b0/8617991/9e7945edb1d4/jpm-11-01177-g001.jpg

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