Sharp Downregulation of Hub Genes Associated With the Pathogenesis of Breast Cancer From Ductal Carcinoma In Situ to Invasive Ductal Carcinoma

Author:

Wang Yao,Liang Faqing,Zhou Yuting,Qiu Juanjuan,Lv Qing,Du Zhenggui

Abstract

IntroductionBreast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.MethodsLaser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.ResultsTwo modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e−07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e–12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.ConclusionsFive hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.

Publisher

Frontiers Media SA

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3