Research Paper Volume 16, Issue 7 pp 5967—5986
Identification and validation of DHCR7 as a diagnostic biomarker involved in the proliferation and mitochondrial function of breast cancer
- 1 Department of Surgical Oncology, Shaanxi Provincial People’s Hospital, Shaanxi, China
- 2 Department of Clinical Laboratory, Affiliated Hospital of Yan’an University, Shaanxi, China
- 3 Department of Health Examination Center, Shaanxi Provincial People’s Hospital, Shaanxi, China
- 4 Department of Breast Disease Center, Shaanxi Provincial Tumor Hospital, Shaanxi, China
- 5 Department of Geriatric Neurology, Shaanxi Provincial People’s Hospital, Shaanxi, China
- 6 Department of Pathology, Affiliated Hospital of Yan’an University, Shaanxi, China
Received: September 18, 2023 Accepted: February 20, 2024 Published: March 22, 2024
https://doi.org/10.18632/aging.205683How to Cite
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Energy metabolism has a complex intersection with pathogenesis and development of breast cancer (BC). This allows for the possibility of identifying energy-metabolism-related genes (EMRGs) as novel prognostic biomarkers for BC. 7-dehydrocholesterol reductase (DHCR7) is a key enzyme of cholesterol biosynthesis involved in many cancers, and in this paper, we investigate the effects of DHCR7 on the proliferation and mitochondrial function of BC.
Methods: EMRGs were identified from the Gene Expression Omnibus (GEO) and MSigDB databases using bioinformatics methods. Key EMRGs of BC were then identified and validated by functional enrichment analysis, interaction analysis, weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Cox analysis, and immune infiltration. Western blot, qRT-PCR, immunohistochemistry (IHC), MTT assay, colony formation assay and flow cytometry assay were then used to analyze DHCR7 expression and its biological effects on BC cells.
Results: We identified 31 EMRGs in BC. These 31 EMRGs and related transcription factors (TFs), miRNAs, and drugs were enriched in glycerophospholipid metabolism, glycoprotein metabolic process, breast cancer, and cell cycle. Crucially, DHCR7 was a key EMRG in BC identified and validated by WGCNA, LASSO regression and receiver operating characteristic (ROC) curve analysis. High DHCR7 expression was significantly associated with tumor immune infiltration level, pathological M, and poor prognosis in BC. In addition, DHCR7 knockdown inhibited cell proliferation, induced apoptosis and affected mitochondrial function in BC cells.
Conclusions: DHCR7 was found to be a key EMRG up-regulated in BC cells. This study is the first to our knowledge to report that DHCR7 acts as an oncogene in BC, which might become a novel therapeutic target for BC patients.
Abbreviations
BC: Breast cancer; EMRGs: Energy-metabolism-related genes; DEGs: Differentially expressed genes; DHCR7: 7-dehydrocholesterol reductase; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; WGCNA: Weighted gene co-expression network analysis; IHC: Immunohistochemistry; TF: Transcription factor; ROC: Receiver operating characteristic; TNBC: Triple-negative breast cancer; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene set enrichment analysis; ROS: Reactive oxygen species; MMP: Mitochondrial membrane potential.