ABERRANT EXPRESSION OF COL14A1, CELRS3, and CTHRC1 IN BREAST CANCER СELLS.

Abstract

Background: Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling.

Aim: To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC.

Materials and methods: The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients.

Results: Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs and members of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes.

Conclusion: The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.