Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker

Abstract

Abstract Purpose: The liver is currently the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characterized biomarkers and mechanisms underlying liver metastasis in BC remain unclear. Methods: The GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to annotate these DEGs and understand the biological functions they are involved in. A protein–protein interaction (PPI) network was constructed to identify hub genes. Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1expression in BC tissues and cell lines was verified (RT-qPCR). SPARCL1 knockdown was performed using siRNAs; its biological function in BC cells was then investigated. Results: We identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. SPARCL1was related to patient prognosis, and its expression in BC was associated with age, TNM stage, estrogen receptor (ER) status, progesterone receptor (PR) status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. In vitro SPARCL1 inhibition promoted BC cell proliferation and migration. Conclusion: We identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.