Disease-Associated Risk Variants and Expression Levels of the lncRNA, CDKN2B-AS1, Are Associated With the Progression of HCC

Abstract

The most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies are located in non-coding regions. The antisense non-coding RNA at the INK4 locus (ANRIL), also known as cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), is a long non-coding (lnc)RNA situated within and antisense to genes encoding CDKN2A/B on chromosome 9p21.3. Single-nucleotide polymorphisms (SNPs) within CDKN2B-AS1 are associated with several cancer types, but their impacts on HCC remain unclear. In this study, we investigated the effects of CDKN2B-AS1 SNPs on both the susceptibility to HCC and its clinicopathological development. Five CDKN2B-AS1 SNP loci—rs564398 (T/C), rs1333048 (A/C), rs1537373 (G/T), rs2151280 (A/G) and rs8181047 (G/A)—were analysed using a TaqMan allelic discrimination assay for genotyping in a cohort of 810 HCC patients and 1190 healthy controls. Under the dominant model, HCC patients with at least one minor C-allele of rs564398 showed a lower risk of liver cirrhosis (odds ratio (OR) = 0.677). Additionally, HCC patients with the GT + TT genotype of rs1537373 had a reduced risk of developing large tumours (T3 + T4) and advanced clinical stages (III/IV), particularly in the male population (OR = 0.644 and 0.679). Furthermore, data from The Cancer Genome Atlas revealed that CDKN2B-AS1 expression levels were elevated in HCC tissues compared to normal tissues and were correlated with advanced T stages, high histological grades and poor prognoses. Our findings suggest that CDKN2B-AS1 levels and its polymorphic variants at rs564398 and rs1537373 may influence the clinicopathological development and progression of HCC in a Taiwanese population.