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Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a rare, understudied primary hepatic malignancy with dismal outcomes. Aiming to identify prognostically relevant single-nucleotide polymorphisms, we analyzed 11 genetic variants with a role in tumor-promoting inflammation (VEGF, EGF, EGFR, IL-1B, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and PTGS2 (COX-2) genes) and their association with disease-free (DFS) and overall survival (OS) in patients undergoing curative-intent surgery for iCCA. Genomic DNA was isolated from 112 patients (64 female, 48 male) with iCCA. Germline polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism protocols. The IL-1B +3954 C/C (73/112, hazard ratio (HR) = 1.735, p = 0.012) and the IL-8 -251 T/A or A/A (53/112 and 16/112, HR = 2.001 and 1.1777, p = 0.026) genotypes were associated with shorter OS in univariable and multivariable analysis. The IL-1B +3954 polymorphism was also associated with shorter DFS (HR = 1.983, p = 0.012), but this effect was not sustained in the multivariable model. A genetic risk model of 0, 1 and 2 unfavorable alleles was established and confirmed in multivariable analysis. This study supports the prognostic role of the IL-1B C+3954T and the IL-8 T-251A variant as outcome markers in iCCA patients, identifying patient subgroups at higher risk for dismal clinical outcomes.
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1 Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662); University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
2 University Hospital RWTH Aachen, Institute of Pathology, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
3 University Hospital RWTH Aachen, Department of Internal Medicine III, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
4 Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662); University Hospital RWTH Aachen, Department of Internal Medicine III, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
5 University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
6 University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507); Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Department of Surgery, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662)