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.

Details

Title
Genetic polymorphisms in interleukin-1β (rs1143634) and interleukin-8 (rs4073) are associated with survival after resection of intrahepatic cholangiocarcinoma
Author
Lurje, Isabella 1 ; Gaisa, Nadine Therese 2 ; Dahl, Edgar 2 ; Knüchel, Ruth 2 ; Strnad, Pavel 3 ; Trautwein, Christian 3 ; Tacke, Frank 4 ; Neumann, Ulf Peter 5 ; Czigany, Zoltan 6 ; Lurje, Georg 6 

 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) 
 University Hospital RWTH Aachen, Institute of Pathology, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507) 
 University Hospital RWTH Aachen, Department of Internal Medicine III, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507) 
 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) 
 University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507) 
 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) 
Pages
12283
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2843248620
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.