Supplementary Material for: Genetic variant of CXCR1 (rs2234671) associates with clinical outcome in perihilar cholangiocarcinoma

Background Perihilar cholangiocarcinoma (pCCA) is a rare primary liver malignancy. Even in patients amenable to surgery, outcomes are often dismal. Here, we aimed to identify prognostic markers for patient outcomes by analyzing functionally relevant single-nucleotide polymorphisms (SNPs) in genes with a role in tumor inflammation and angiogenesis. We analyzed 11 polymorphisms in the inflammation-angiogenesis axis (VEGF, EGF, EGFR, IL-1b, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and COX2 genes) for their prediction of tumor recurrence and survival in pCCA patients undergoing surgery in a curative intent. Methods Samples were obtained from 111 patients with pCCA undergoing liver resection in curative intent. DNA was extracted and analyzed using PCR-RFLP protocols and correlated with patients’ outcomes. Results Out of the assessed variants, only the CXCR1 (also: Interleukine-8-receptor alpha – IL-8RA) +860 C>G heterozygous polymorphism (rs2234671) was associated with decreased disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) (18/111 (16.2%), median DFS 14 months, log-rank p=0.007, median CCS 31 months, log-rank p=0.007, median OS 6 months, log-rank p=0.002), compared to the GG genotype (92/111 (82.9%), median DFS 55 months, median CCS 63 months, median OS 33 months). In multivariate analysis, +860 C>G remained an independent prognostic factor for DFS (adjusted p=0.008), CCS (adjusted p=0.001) and OS (adjusted p=0.001). Conclusion Genetic variant of CXCR1 +860 C>G may serve as a molecular marker for DFS, CSS and OS in patients undergoing curative-intent surgery for pCCA, indicating that the analysis of SNPs in genes involved in immune-mediated angiogenesis may help to identify patient subgroups at high risk for dismal oncological and overall outcome.