Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis.

ABSTRACT

Emerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (LINC-ROR) is aberrantly expressed in several types of cancer, including colon cancer (CC). LINC-ROR intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the potential association of LINC-ROR (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, p = 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, p = 0.003), homozygote (OR = 5.0, 95%CI = 1.69-14.29, p = 0.003), dominant (OR = 3.33, 95%CI = 1.20-9.09, p = 0.003), and recessive (OR = 2.63, 95%CI = 1.37-5.0, p = 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 LINC-ROR (rs1942347) variant with CC prognosis.