Comparative Transcriptome Analysis of Peripheral Blood Mononuclear Cells Across Clinical Cohorts of Hepatitis B Virus Induced Hepatocellular Carcinoma and Chronic Asymptomatic Hepatitis B Infection in Nigeria
Hepatitis B Virus (HBV) infection affects about 20 million Nigerians and its most fatal complications is the hepatocellular carcinoma (HCC). Chronic hepatitis B (CHB) infection progresses to HCC which lacks sensitive and specific biomarkers at early stage for detection and subsequent treatment. Efforts in this study is therefore to assess the differential gene expression across clinical cohorts of HBV infection to identify the potential biomarkers of early-stage HCC. Total RNA was extracted and the peripheral blood mononuclear cells (PBMC) in 12 samples were sequenced through the bulk RNA sequencing modality. This was followed by bioinformatic analysis for differential gene expression studies using GALAXY, Qiagen RNA-Sequencing Analysis and DAVID pipelines. Transcriptomic analysis of the PBMC identified a total of 66,726 genes and transcripts. Among patients with HBV-Induced HCC vs CHB, a total of 3,204 genes were differentially expressed with 76 and 272 genes significantly upregulated and downregulated respectively. Across the clinical cohorts of HBV-induced HCC vs healthy controls, 4561 were dysregulated with 370 and 375 genes significantly upregulated and downregulated respectively. Across the significantly upregulated genes of the cohort HBV-induced HCC vs healthy controls, 86 Gene ontology (GO) terms were identified, 19 clustered, 103 terms did not cluster, while across the downregulated cohort, 255 GO terms were identified, 63 clustered, 335 did not. The mitogen-activated protein kinase (MAPK) signalling pathway, cell division cycle and microRNA pathways in the HCC cohort were dysregulated Overall design: To investigate the differential gene expression profiles across clinical cohorts of patients with HBV-induced hepatocellular carcinoma, chronic hepatitis B and healthy controls. We recruited 36 patients and subsequently divided the subjects into sequencing cohort (n=12) and validation cohort (n=24). We conducted gene expression profiling studies from data obtained from the HBV-induced HCC, chronic asymptomatic HBV patients and healthy controls. Differential gene expression profile analysis of the RNA-seq data from the 12 samples were studied using GALAXY and DAVID pipeline.