The Obesity-Related Metabolic Gene HSD17B8 Protects Against Breast Cancer: High RNA/Protein Expression Means a Better Prognosis.

Abstract

BackgroundThe incidence of breast cancer is increasing annually. Obesity and metabolism are considered risk factors for breast cancer. Discovery of obesity- and metabolism-related breast cancer prognostic genes is imminent.Material/MethodsWe screened metabolism-related genes (MRG) from KEGG and downloaded the obese female dataset GSE151839 from GEO, which screened differentially-expressed genes (DEGs), seen as female obesity-related genes. The intersection of MRGs and DEGs was obesity-related metabolic genes (OMGs), verified by enrichment analysis. After downloading breast cancer data from TCGA, univariate Cox regression and log-rank P analyses were used to screen hub OMGs related to breast cancer prognosis. ROC curve and Kaplan-Meier (KM) plotter, GEPIA, and GENT2 databases were used to verify the hub OMGs at the RNA level. CPTAC and HLA databases were used to verify the hub OMGs at the protein level.ResultsWe screened 33 OMGs. The results of univariate Cox regression and log-rank P analysis showed 3 of 33 OMGs (ABCA1, LPIN1, HSD17B8) were associated with the prognosis of breast cancer patients. After verification with ROC, KM-plotter, and GEPIA, only HSD17B8 was related to breast cancer prognosis (overall/disease-free survival). Results of GENT2 showed the RNA expression of HSD17B8 in breast cancer subtypes with poor prognosis is significantly lower than that with good prognosis. Results of CPTAC and HLA databases showed that the protein expression level of HSD17B8 in breast cancer tissues was significantly lower than that in adjacent normal tissues.ConclusionsHSD17B8 is a protective gene against breast cancer. The higher the expression of HSD17B8, the better the prognosis of breast cancer patients.