Inflammation and RNA-Related Polymorphisms in Resected Cholangiocarcinoma: Prognostic Associations in Intrahepatic
Guanwu Wang1,2, Dong Liu1,3, Tarick M Al-Masri1,4
1Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
Background:
Cholangiocarcinoma (CCA) is a heterogeneous and aggressive malignancy of the biliary tract, often classified into intrahepatic (iCCA) and perihilar (pCCA) subtypes. Inflammatory and RNA-regulatory pathways are implicated in CCA pathogenesis. However, the prognostic significance of related single nucleotide polymorphisms (SNPs) remains unclear.
Method:
We retrospectively analyzed nine candidate SNPs in inflammation- and RNA-related genes (IL4 rs2243250, IL17A rs4711998, TNIP1 rs7708392, CD274 rs822336, CDKN2B-AS1 rs10965215, NSRP1 rs6505162, MEG3 rs7158663, LOC105370003 rs7315438 and LncRNA PTCSC3 rs944289) in 229 patients with resected CCA (112 iCCA and 117 pCCA). Genotyping was performed using TaqMan assays. Associations between SNP genotypes and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression analyses stratified by anatomical subtype.
Results:
The study cohort comprised 229 patients undergoing curative-intent resection for CCA, including 112 iCCA and 117 pCCA cases. Median follow-up was 63 months for iCCA and 89 months for pCCA. Tumor recurrence occurred in 68.8% of iCCA and 54.7% of pCCA patients. No significant associations between SNP genotypes and clinical outcomes were identified in the pCCA cohort. In iCCA, isolated associations with overall survival were observed for TNIP1 rs7708392 and NSRP1 rs6505162, but these findings were not consistently supported across analyses and were limited by small subgroup sizes. No SNP demonstrated consistent associations with recurrence-free survival or cancer-specific survival.
Conclusion:
The investigated inflammation- and RNA-related SNPs showed no clinically relevant prognostic value in resected cholangiocarcinoma. Independent validation in larger multicenter cohorts remains warranted.
