Exploration of the Shared Gene and Molecular Mechanisms between Breast Cancer and Non-alcoholic Fatty Liver Disease Based on Available Public Transcriptome Sequencing Data

Abstract

Background: Breast cancer (BC) is one of the most common malignant tumors in women; its etiology is unknown. A meta-analysis demonstrates a close association between non-alcoholic fatty liver disease (NAFLD) and BC. However, the mechanism of their association remained unknown. The present study aimed to investigate the associations between BC and NAFLD. Method: The transcriptome sequence data on BC and NAFLD were downloaded from the The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. The co-expression modules related to BC and NAFLD were identified using Weighted Gene Co-Expression Network Analysis (WGCNA). ClueGo software was used for enrichment analysis on BC and NAFLD common genes. Moreover, the common microRNAs (miRNAs) in BC and NAFLD were obtained from the Human microRNA Disease Database (HMDD), and the target genes of these miRNAs were predicted using the miRTarbase. Disease enrichment was performed using lncRNA from the Starbase. We then constructed the common miRNAs–mRNAs network. In addition, we obtained a correlation analysis of common genes and BC unique genes. Result: Several modules were identified as significant with BC and NAFLD based on WGCNA results. ClueGO enrichment analysis revealed that vasculature development is a feature shared by the pathophysiology of BC and NAFLD. The miRNA enrichment BP and lncRNA disease enrichment analyses revealed a link between BC and NAFLD. Furthermore, we identified three BC features that may be involved in the transition from NAFLD to BC and disease-crucial genes FOXO1 and PKD2. Conclusion: Our study revealed that vasculature development may be an important point for BC and NAFLD, with parts of BC patients evolving from NAFLD by three group feature genes. Furthermore, these gene modules could be biomarkers or potential diagnostic targets in NAFLD patients.