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
Genetic polymorphisms could be biomarkers for cancer risk and prognosis. Recent years, it was found that coding genes and non-coding genes had single nucleotide polymorphisms (SNPs). LncRNAs had important roles in the tumor incidence, progression, and prognosis. Thus, lncRNA polymorphisms had potential to be biomarkers for cancer precaution and prognostic prediction.
The aim of this study is to screen out the effective biomarkers for the hepatocellular cancer (HCC) risk and prognosis. The selected polymorphisms would have potential for the prediction of cancer risk and prognosis.
Five hundred and twenty-one patients of HCC and frequency matched 817 controls were studied for the cancer risk study. Among them, 351 patients for which the information was all available were recruited for the prognosis study. Then, 68 HCC specimens and corresponding samples from the noncancerous region were detected for the expression level study.
For the risk and prognosis study, the samples were detected by the genomic DNA extracted and allele-specific PCR with KASPar reagents. The single nucleotide polymorphisms were selected by the Haploview software. The expression level study isolated the RNA isolated and then converted it to cDNA. The SYBR based real-time PCR were adopted for the lncRNA expression.
We found the HOTTIP rs17501292, rs2067087, and rs17427960 SNPs increased HCC risk by 1.55-, 1.20-, and 1.18-fold under an allelic model, and the MALAT1 rs4102217 SNP increased HCC risk by 1.32-fold under a dominant model. In addition, the two-way interaction of HOTTIP rs17501292 and MALAT1 rs619586 polymorphisms decreased HCC risk and exhibited epistatic effects. In the survival analysis, the HOTTIP rs3807598 variant genotype showed significantly longer survival time in the hepatitis B virus (HBV)-negative subgroup, and MALAT1 rs591291 showed an association with significantly better prognosis in the female and HBV-negative group. In this study, no significant effect in eQTL analysis was observed.
Some specific HOTTIP and MALAT1 SNPs have the potential to be biomarkers for HCC risk and prognosis.
Screening SNPs could be valuable for the identification of biomarkers for HCC risk and prognosis. It could also be used for patient care, as there would be a cohort of patients who would benefit from screening using these positive SNPs.