Dysregulated cholesterol regulatory genes as a diagnostic biomarker for cancer.

A dysregulation of cholesterol homeostasis is often seen in various cancer cell types, and elevated cholesterol content and its metabolites appear to be crucial for cancer progression and metastasis. Cholesterol is a precursor of various steroid hormones and a key plasma membrane component especially in lipid-rafts which also modulates many intracellular signaling pathways. To provide an insight of dysregulated cholesterol regulatory genes, their transcript levels were analyzed in different cancers and their influence was correlated with the overall survival of cancer patients using cancer data base analysis. This analysis found a set of genes (e.g., ACAT1, RXRA, SOAT1 and SQLE) which were not only often dysregulated but had also been associated with poorer overall survival in most cancer types. qRT-PCR analysis has found elevated SQLE and SOAT1 transcript levels, and downregulated expressions of RXRA and ACAT1genes in triple negative breast cancer tissues as compared to adjacent control tissues, indicating this dysregulated expression of the gene signature as a diagnostic marker for breast cancer. This study, for the first time, identified a gene signature associated with the dysregulation of cholesterol homeostasis in cancer cells which may not only be used as a diagnostic/prognostic marker, but also be promising drug targets for the advancement of cancer therapy.