Altered expression level of ACSM5 in breast cancer: An integrative analysis of tissue biomarkers with diagnostic potential

Abstract

BackgroundAbnormal gene expression levels of enzymes involved in fatty acid synthesis and oxidation pathways in breast cancer have been shown to associate with progression of breast cancer. However, little is known about the significance of alternations in fatty acid activation, as a key step in their metabolism. We aimed to recognize suitable biomarkers indicating the altered activation of fatty acids and examine their differential expression in breast cancer and adjacent normal breast tissue samples. Material and methodsTranscript levels of ACS enzymes were analyzed in TCGA data (RNAseq), breast cancer and normal breast samples by differential gene expression (DGE). Gene set enrichment analysis (GSEA) was performed to highlight the most enriched genes involved in the activation of fatty acids. Bioinformatic analysis was performed for the selection of LncRNAs. Gene expression analyses were performed using quantitative Real-time PCR (qRT-PCR) in breast cancer tissue samples and adjacent normal breast tissue samples. Correlation and survival analyses were performed using R program. ROC curves were created for TCGA and qPCR data to evaluate the prognostic potential of the biomarkers. ResultsGSEA analysis revealed that ACSM5 is highly enriched in normal breast tissue samples compared to breast cancer tissue samples. LINC00265 with highest co-efficient score with ACSM5 was selected for further analyses. The expression level of ACSM5 and LINC00265 positively correlated with each other and were significantly low in breast cancer tissues compared to normal breast tissues. Correlation analysis suggested a positive correlation between ACSM5 and LINC00265 genes. Survival analysis predicted prognostic potential for ACSM5. ROC curve analyses revealed that ACSM5 and LINC00265 can distinguish breast tumor samples from adjacent breast tissues. ConclusionOur study suggests ACSM5 gene as a potential biomarker with prognostic value in detection of altered activation of medium-chain fatty acids in breast cancer. In addition, the positive correlation between ACSM5 and LINC00265 suggests the presence of possible regulatory mechanism between them.