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Expression of genes associated with poor prognosis from hepatocellular carcinoma are increased in peripheral blood from Hmong with active hepatitis B infection

ABSTRACT: BACKGORUND & AIMS: Hepatocellular carcinoma (HCC) disproportionally affects Asian Americans due to the high prevalence of chronic hepatitis B virus (HBV) infection and among Asian ethnic groups. The Hmong are diagnosed with HCC at a younger age, with more advanced stage disease, and have the highest cause specific mortality of any Asian ethnic group. Poor survival from HCC has also been associated with differential gene expression in HCC tumors leading us to hypothesize that quantitative traits loci lead to differences in the expression of genes in Hmong which reduce their HCC survival. METHODS: We performed bulk RNA-sequencing of whole blood total RNA from HBV-infected Hmong (n=30) and non-Hmong Asians (Chinese (n=46), and Vietnamese (n=19)). RESULTS: No significant differences between groups were identified in demographic, clinical, or viral factors. A total of 1,491 differentially-expressed transcripts (DETs) were identified across the 3 ethnic groups. When restricted to those with an HBV viral load >2,000 IU/L, 768 DETs were identified and accurately separated individuals by ethincity. Among 273 DETs identified by functional enrichment and pathway analysis and associated with annotated sets of HCC-related genes, 9 were found in 2 gene sets highly expressed in HCC with poor survival. After adjusting for age and sex, expression levels of 4 of these, including CD164, ECT2, HDAC2, and UBE2T, remained significantly elevated in Hmong compared to Chinese and Vietnamese. CONCLUSIONS: These results suggest expression quantitative trait loci predispose Hmong to a more agrressive form of HCC and may explain the poor survival among this Asian ethnic group.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173897 | GEO | 2021/11/01

REPOSITORIES: GEO

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Project description:RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related HCC has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from Chinese HBV-related hepatocelluar carcinoma patients using 36bp single-end sequencing approach on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify > 50% of all the annotated genes for each sample. Furthermore, from by far the largest database of transcripts expressed in HCC tissues, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism-related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3-24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene levels and exon levels, implying a much complex landscape of transcript-specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 (ATPase family, AAA domain containing 2) gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of the HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system-wide levels. A comprehensive analysis of transcriptome for 10 match-paired HBV-related Chinese HCC and non-cancerous adjacent tissues. Processed data files: Exon-level results, gene-level results, differentially expressed exons, and differently expressed genes (DEGs).

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Expression of genes associated with poor prognosis from hepatocellular carcinoma are increased in peripheral blood from Hmong with active hepatitis B infection

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