Abstract
Emerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (
) is aberrantly expressed in several types of cancer, including colon cancer (CC).
intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the potential association of
(rs1942347) with the clinicopathological features and outcome of CC cases. Archived FFPE (n = 180) CC samples were enrolled. Taq-Man allelic discrimination PCR was used for genotyping in propensity-matched cohorts with/without positive staining for mutant BRAF protein after eliminating confounders bias. The rs1942347*A allele variant was associated with high pathological grade, larger tumor size, distant metastasis, and mortality. Multiple logistic regression analysis adjusted by sex and BRAF mutation showed A/A genotype carriers to have 3 times more risk of early onset of cancer (OR = 3.13, 95%CI = 1.28-7.69,
= 0.034) than T/T genotype carriers. Overall analysis showed that rs1942347*A allele carriers had higher risk of mortality under heterozygote (OR = 2.13, 95%CI = 1.08-4.35,
= 0.003), homozygote (OR = 5.0, 95%CI = 1.69-14.29,
= 0.003), dominant (OR = 3.33, 95%CI = 1.20-9.09,
= 0.003), and recessive (OR = 2.63, 95%CI = 1.37-5.0,
= 0.011) models compared to T/T allele carriers. Stratified analysis by BRAF status revealed that the ancestor T/T allele conferred protection in BRAF mutant CC patients and was associated with a 73-93% reduced risk of mortality under heterozygote/homozygote comparison models. Using Kaplan-Meier curves, carriers of the A/A genotype had shorter survival times than T/T cohorts. The univariate Cox regression model revealed that the A/A genotype was associated with a 3.5 times greater mortality risk than the T/T genotype. However, after adjustment by multiple Cox regression analysis, the risk was insignificant. In conclusion, this is the first study identifying the potential association of the
(rs1942347) variant with CC prognosis.