Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis.

Abstract

Introduction: Breast cancer (BC) is the most prevalent cancer among women globally. Metastasis is the leading cause of mortality in most cancers. Early BC detection before metastasis can enhance survival rates. Understanding BC metastasis mechanisms could aid in developing metastasis-specific treatments.

Method: The role of long non-coding RNAs (lncRNA) in cancer progression is recognized, yet the importance of specific lncRNAs in BC, despite potential alterations, remains inadequately explored. We utilized bioinformatics tools to identify novel lncRNAs dysregulated in metastasis. To achieve this objective, the gene expression profile of GSE102484, encompassing metastatic and non-metastatic BC tissue samples, was analyzed using the limma package in R with cut-off criteria set at an adjusted p-value < 0.005 and |fold change (FC)| ≥ 0.5. We used WGCNA analysis to find co-expression genes for lncRNAs. Then, we identified hub genes and performed pathway enrichment to better understand the results. Considering the defined criteria, eight novels of dysregulated lncRNAs and top 10 miRNAs were identified.

Result: Dysregulated lncRNAs are found in yellow, green, brown, purple, and turquoise co-expression modules from WGCNA analysis. Enrichment analysis of these co-expressed modules revealed relevant pathways to metastasis, such as epithelial-to-mesenchymal transition and integrin cell-surface interactions, as well as regulation of HIF1-alpha. In addition, SDPR, TGFB1I1, ILF3, KIF4A, and COL5A1 were identified as hub genes. Based on DElncRNA-miRNADEmRNA connections and co-expression, we ultimately constructed lncRNA-associated ceRNA axes.

Conclusion: The current study may identify novel lncRNAs implicated in BC metastasis; still, additional research is required to determine the potential functions of these lncRNAs in BC metastasis.