Integrative transcriptomic analysis and validation of non-coding RNA in liver cancers

Abstract

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the most common and cause cancer-related deaths. Due to the lack of sensitivity and specificity of conventional markers, such as AFP, CA19-9 and CEA. Thus, this study aimed to identify miRNAs as a diagnostic biomarker for HCC and iCCA. First, in discovery set, RNA sequencing and small RNA sequencing data of 992 HCC and adjacent tissues and 116 iCCA and adjacent tissues were downloaded from the GEO database. After that, the lncRNA-miRNA-mRNA network was constructed and analyzed for the differential expression of lncRNA (DElncRNA), miRNA (DEmiRNA), and mRNA (DEmRNA). Then, the significant DEmiRNAs from the network were compared to miRNA data from the TCGA database. The significant differences in miRNA expression of tumor tissues compared to adjacent tissues from the TCGA database were selected according to the inclusion criteria including fold change and P-value <0.05. In validation set, there were three serum miRNAs in HCC, including miR-122-5p, miR-182-5p, and miR-199b-3p were found to be upregulated in HCC when compared to the CHB group. In addition, there were four serum miRNAs in iCCA, including miR-139-3p, miR-148a-3p, miR-221-3p, and miR-222-3p, were significantly higher in iCCA patients when compared to healthy controls. Moreover, ROC curves of candidate miRNAs were analyzed. The result showed area under the curve (AUC) of 0.67, 0.62 and 0.54 for miR-199b-3p, miR-122-5p, miR-182-5p, respectively. In addition, in iCCA, AUC was 0.99, 0.90, 0.87 and 0.86 for miR-222-3p, miR-221-3p, miR-148a-3p and miR-139-3p, respectively. In conclusion, serum miR-122-5p, and miR-199b-3p could potentially serve as diagnostic biomarkers for HCC. And serum miR-139-3p, miR-148a-3p, miR-221-3p, and miR-222-3p could potentially serve as diagnostic biomarkers for the iCCA.