Published online Jun 21, 2018. doi: 10.3748/wjg.v24.i23.2482
Peer-review started: March 23, 2018
First decision: April 10, 2018
Revised: April 17, 2018
Accepted: May 18, 2018
Article in press: May 18, 2018
Published online: June 21, 2018
Processing time: 84 Days and 19.2 Hours
To evaluate the association of 12 tag single nucleotide polymorphisms (tagSNPs) in three onco-long non-coding RNA (lncRNA) genes (HOTTIP, CCAT2, MALAT1) with the risk and prognosis of hepatocellular cancer (HCC).
Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples, including 521 HCC patients and frequency-matched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital of China Medical University from 2012-2015. The expression quantitative trait loci (eQTL) analyses were conducted to explore further the potential function of the promising SNPs.
Three SNPs in HOTTIP, one promoter SNP in MALAT1, and one haplotype of HOTTIP were associated with HCC risk. The HOTTIP rs17501292, rs2067087, and rs17427960 SNPs were increased to 1.55-, 1.20-, and 1.18-fold HCC risk under allelic models (P = 0.012, 0.017 and 0.049, respectively). MALAT1 rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models (P = 0.028). In addition, the two-way interaction of HOTTIP rs17501292-MALAT1 rs619586 polymorphisms showed a decreased effect on HCC risk (Pinteraction = 0.028, OR = 0.30) and epistasis with each other. HOTTIP rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup (P = 0.049, HR = 0.12), and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups (P = 0.022, HR = 0.37; P = 0.042, HR = 0.25, respectively). In the study, no significant effect was observed in eQTL analysis.
Specific lncRNA (HOTTIP and MALAT1) SNPs have potential to be biomarkers for HCC risk and prognosis.
Core tip: We aim to evaluate the association of twelve tag single nucleotide polymorphisms (tagSNPs) in three onco-lncRNA genes (HOTTIP, CCAT2, MALAT1) with the risk and prognosis of hepatocellular cancer (HCC). Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples. We found three SNPs in HOTTIP, one promoter SNP in MALAT1 and one haplotype of HOTTIP gene were associated with HCC risk. In addition, HOTTIP rs3807598 variant genotype showed significantly longer survival time in hepatitis B virus (HBV) negative subgroup, and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups.