Bioinformatics and qPCR analyses of laminins’ cognate receptors in cholangiocarcinoma tissues reveal the integrin ITGB4 as a potential biomarker

Abstract

Cholangiocarcinoma (CCA), a devastating epithelial tumor arising in bile ducts with dismal prognosis and high mortality rate, has the highest worldwide incidence in Northeastern Thailand, raising a serious health public concern to the country. Due to a desmoplastic nature of CCA, understanding CCA cell-matrix interaction is necessitated. Here, an in silico analysis using two RNA-sequencing (Pan-Cancer Analysis of Whole Genomes and The Cancer Genome Atlas) databases and ten microarray datasets from the Gene Expression Omnibus database, was utilized to compare the mRNA expression of 19 genes of laminins’ cognate receptors between CCA and adjacent noncancerous tissues. The results were further validated in tissues of Thai patients using qPCR analysis. Bioinformatics analyses revealed that there were five common dysregulated genes in the three transcriptomic databases, in which four were upregulated genes (ITGAV, ITGA2, ITGB1, and ITGB4), and one was downregulated gene (SDC2). Of these differentially expressed genes, qPCR analysis confirmed the elevated mRNA expression of ITGB4 encoding integrin β4 in 97% of the CCA cases and pinpointing the ITGB4 as a potential diagnostic biomarker for CCA.