Upregulation of Differentiates Intrahepatic Cholangiocarcinoma from Hepatocellular Carcinoma and Both Colorectal and Pancreatic Adenocarcinoma Liver Metastases.

Background: Altered gene expression in cancers holds great potential to improve the diagnostics and differentiation of primary and metastatic liver cancers. In this study, the expression of the protein-coding genes ring finger protein 135 (), ephrin-B2 (), ring finger protein 125 (), homeobox-C 4 (), actin-binding LIM protein 1 () and oncostatin M receptor () and the long non-coding RNAs (lncRNA) prospero homeobox 1 antisense RNA 1 () and leukemia inhibitory factor receptor antisense RNA 1 () was investigated in hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and pancreatic ductal adenocarcinoma liver metastases.

Methods: This study included 149 formalin-fixed, paraffin-embedded samples from 80 patients. After RNA isolation, quantification, reverse transcription and preamplification, real-time qPCR was performed. The gene expression between different groups was calculated relative to the expression of the reference genes using the ∆∆Cq method and statistically analyzed. The expression of the genes was additionally analyzed using the AmiCA and UCSC Xena platforms.

Results: In primary cancers, our results showed differential expression between primary tumors and healthy tissues for all the genes and lncRNA examined. Moreover, we found downregulation of in hepatocellular carcinoma, downregulation of in colorectal liver metastases and upregulation of in cholangiocarcinoma compared to primary liver cancers and metastatic cancers. The major finding is the upregulation of in cholangiocarcinoma compared to hepatocellular carcinoma, colorectal liver metastases, pancreatic ductal adenocarcinoma liver metastases and healthy liver tissue. We propose as a potential biomarker that differentiates cholangiocarcinoma from other cancers and healthy liver tissue.

Conclusions: This study emphasizes the importance of understanding the differences in gene expression between healthy tissues and primary and metastatic cancers and highlights the potential use of altered gene expression as a diagnostic biomarker in these malignancies.