RNA biotype-associated molecular classification in hepatitis B-related hepatocellular carcinoma

Recent advance of RNA-seq technology enabled us to profile the diverse variations of RNA transcripts precisely, including the variants from alternative splicing as well as non-coding transcripts. Here, by performing transcriptome profiling including coding and noncoding transcripts, we identify four molecular subtypes of hepatitis B-related hepatocellular carcinoma (HCC) patients that are characterized by enriched expression of the RNA biotypes of noncoding (NC) and immune-related transcripts (IM) (i.e., IM+NC+, IM-NC+, IM+NC-, IM-NC-). The subtype IM+NC+ shows better prognostic outcome, while the subtype IM+NC- shows the worst prognostic outcome, respectively. Further interrogation of the subtypes identifies long noncoding transcripts (i.e., LINC00844, C3P1, and TRPG1-AS1) as well as an alternatively spliced event of USO1 that play pivotal roles in HCC progression. In addition, we report an oncogenic fusion transcript SLC39A14-PIWIL2 that promotes an aggressive phenotype of HCC. Our comprehensive and systematic analysis of HCC transcriptome identify RNA biotype-based molecular classification, revealing novel driver transcriptome variants that can be potential biomarkers and/or therapeutic targets for precision medicine. Transcriptome profiling from 68 cases of HCC tissues and 10 adjacent non-tumoral tissues were performed. Four subtypes: S1: IM+NC+ S2: IM-NC+ S3: IM+NC- S4: IM-NC-