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

SIMPLE SUMMARY: Biliary tract cancer (BTC) is a primary liver malignancy with poor outcome. The identification of the ideal surgical candidates is often challenging and stratification algorithms comprising the parameters of individual tumor biology are missing. Here, we investigated a potential role of circulating CXCL1, CXCL10 and CXCL13 in patients with resectable BTC as novel biomarkers and could show that elevated levels of CXCL13 both before and after tumor resection identified a subgroup of patients with significantly impaired outcomes following tumor resection. Thus, the present study supports a fundamental role of the CXC chemokine family in BTC and identifies circulating levels of CXCL13 as a previously unrecognized marker for predicting outcomes following the resection of BTC. 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.