Open AccessEndotrophin, a pro-peptide of Type VI collagen, is a biomarker of survival in cirrhotic patients with hepatocellular carcinoma
Author(s) -
Diana Julie Leeming,
Signe Holm Nielsen,
Roslyn Vongsuvanh,
Pruthviraj Uchila,
Mette Juul Nielsen,
Alexander Lynge Reese-Petersen,
David van der Poorten,
Mohammed Eslam,
Detlef Schuppan,
Morten A. Karsdal,
Jacob George
Publication year - 2021
Publication title -
hepatic oncology
Language(s) - English
Resource type - Journals
eISSN - 2045-0931
pISSN - 2045-0923
DOI - 10.2217/hep-2020-0030
Subject(s) - hepatocellular carcinoma , medicine , gastroenterology , cirrhosis , biomarker , hazard ratio , fibrosis , proportional hazards model , oncology , confidence interval , biochemistry , chemistry
Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients. Patients & methods: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated. Results & conclusion: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05–0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC.