Golgi Protein 73 (GP73) Serum Levels Predict Outcome after Resection of Biliary Tract Cancer

Sven H Loosen; Justus Halpaap; Simon Labuhn; Jan Bednarsch; Patrick H Alizai; Anjali A Roeth; Sven A Lang; Mihael Vucur; Jakob N Kather; Wolfram T Knoefel; Tom F Ulmer; Ulf P Neumann; Christoph Roderburg; Tom Luedde

doi:10.3390/cancers14184428

Golgi Protein 73 (GP73) Serum Levels Predict Outcome after Resection of Biliary Tract Cancer

Cancers (Basel). 2022 Sep 12;14(18):4428. doi: 10.3390/cancers14184428.

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 Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
³ Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
⁴ Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01069 Dresden, Germany.
⁵ Department of General, Visceral and Pediatric Surgery, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.

Abstract

Background: Tumor resection represents the only potentially curative therapy for patients with biliary tract cancer. Nevertheless, disease recurrence is observed in about 50% of patients, leading to a 5-years survival rate of less than 50%. The Golgi protein 73 (GP73), a type II Golgi transmembrane protein, exerts important functions of intracellular protein processing and transportation. Circulating GP73 has recently been suggested as a prognostic marker following resection of hepatocellular carcinoma (HCC) but its role in the context of BTC has remained unknown. In this study, we evaluate a potential role of circulating GP73 as a novel biomarker in patients with resectable BTC.

Methods: GP73 serum levels were measured by immunoassay in n = 97 BTC and n = 40 HCC patients as well as n = 31 healthy controls. Results were correlated with clinical data.

Results: Serum GP73 levels were significantly elevated in BTC patients compared to healthy controls but lower compared to HCC patients. The combination of GP73/CA19-9 showed a sensitivity and specificity of 83.5% and 90.3% regarding the differentiation of BTC patients and healthy controls. BTC patients with baseline GP73 levels above the ideal cut-off value (42.47 ng/mL) showed a significantly reduced median overall survival (193 days) compared to patients with preoperative GP73 levels below this cut-off (882 days). These results were confirmed in uni- and multivariate Cox-regression analysis including several clinicopathological parameters such as age, ECOG performance status, tumor stage as well as established tumor markers and parameters of liver and kidney function.

Conclusions: GP73 represents a previously unrecognized biomarker in the patients with resectable BTC that identifies patients with an impaired postoperative outcome. If larger clinical trials confirmed these findings, measurement of GP73 serum levels might become a novel tool in the challenging preoperative stratification process of patients with resectable BTC.

Keywords: BTC; CCA; biomarker; cholangiocarcinoma; prognosis; surgery.

Grants and funding

Work in the laboratory of T.L. 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 T.L. 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.