Serum Levels of CXCL13 Are an Independent Predictor of Survival Following Resection of Biliary Tract Cancer

Sven H Loosen; Tom F Ulmer; Simon Labuhn; Jan Bednarsch; Sven A Lang; Patrick H Alizai; Anne T Schneider; Mihael Vucur; Ulf P Neumann; Tom Luedde; Christoph Roderburg

doi:10.3390/cancers14174073

Serum Levels of CXCL13 Are an Independent Predictor of Survival Following Resection of Biliary Tract Cancer

Cancers (Basel). 2022 Aug 23;14(17):4073. doi: 10.3390/cancers14174073.

Authors

Affiliations

¹ Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
² Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.

Abstract

Background: The prognosis of biliary tract cancer (BTC) has remained very poor. Although tumor resection represents a potentially curative therapy for selected patients, tumor recurrence is common, and 5-year survival rates have remained below 50%. As stratification algorithms comprising the parameters of individual tumor biology are missing, the identification of ideal patients for extensive tumor surgery is often challenging. The CXC chemokine family exerts decisive functions in cell-cell interactions and has only recently been associated with cancer, but little is known about their function in BTC. Here, we aim to evaluate a potential role of circulating CXCL1, CXCL10 and CXCL13 in patients with resectable BTC.

Methods: Serum levels of CXCL1, CXCL10 and CXCL13 were measured by multiplex immunoassay in a cohort of 119 BTC patients undergoing tumor resection and 50 control samples.

Results: Circulating levels of CXCL1, CXCL10 and CXCL13 were all significantly elevated in BTC patients compared to healthy controls and increased the diagnostic power of established tumor markers such as CA19-9 when used in combination. Importantly, elevated levels of CXCL13 both before and after tumor resection identified a subgroup of patients with significantly impaired outcomes following tumor resection. As such, BTC patients with initial CXCL13 levels above the ideal prognostic cut-off value (25.01 pg/mL) had a median overall survival (OS) of 290 days compared to 969 days for patients with low initial CXCL13 levels. The prognostic value of circulating CXCL13 was further confirmed by uni- and multivariate Cox regression analyses. Finally, the individual kinetics of CXCL13 before and after tumor resection were also indicative of patient outcomes.

Conclusion: Our data support a fundamental role of the CXC chemokine family in BTC and identified circulating levels of CXCL13 as a previously unrecognized marker for predicting outcomes following the resection of BTC.

Keywords: CXC chemokine receptors; biliary tract cancer; biomarker; chemokine (C-X-C motif) ligand; chemokines; cholangiocarcinoma.

Grants and funding

Work in the laboratory of TL was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program through the ERC Consolidator Grant PhaseControl (Grant Agreement 771083). The laboratory of TL was further funded by the German Cancer Aid (Deutsche Krebshilfe—110043 and a Mildred Scheel Professorship), the German Research Foundation (DFG—LU 1360/3-2 (279874820), LU 1360/4-(1461704932) and SFB-CRC 1382), the German Ministry of Health (BMG—DEEP LIVER 2520DAT111) and support from the Medical Faculty of the Heinrich Heine University.