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Blood-based tumor fibrosis markers as diagnostic and prognostic biomarkers in patients with biliary tract cancer.
Christensen, Troels D; Jensen, Christina; Larsen, Ole; Leerhøy, Bonna; Hansen, Carsten P; Madsen, Kasper; Høgdall, Dan; Karsdal, Morten A; Chen, Inna M; Nielsen, Dorte; Johansen, Julia S; Willumsen, Nicholas.
Afiliação
  • Christensen TD; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
  • Jensen C; Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
  • Larsen O; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
  • Leerhøy B; Digestive Disease Center, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
  • Hansen CP; Department of Surgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Madsen K; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
  • Høgdall D; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
  • Karsdal MA; Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
  • Chen IM; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
  • Nielsen D; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
  • Johansen JS; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Willumsen N; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
Int J Cancer ; 152(5): 1036-1049, 2023 03 01.
Article em En | MEDLINE | ID: mdl-36455598
ABSTRACT
Biliary tract cancer (BTC) is characterized by a desmoplastic extracellular matrix (ECM). We tested the diagnostic and prognostic use of seven circulating biomarkers of ECM remodeling pro-peptides of type III collagen (PRO-C3), VI (PRO-C6) and XI (PRO-C11), matrix metalloprotease (MMP) degraded type III collagen (C3M) and type IV collagen (C4M) fragments, granzyme B degraded type IV collagen fragments (C4G) and MMP degraded and citrullinated vimentin (VICM) a marker of macrophage activation. The study included 269 patients with all stages of BTC and 49 patients with benign biliary tract diseases. Serum samples from BTC patients were collected before surgery, or before first- or second-line chemotherapy. C3M, C4M, PRO-C3, PRO-C6, PRO-C11 and VICM levels were elevated in patients with BTC compared to patients with benign disease. Receiver operating characteristics curve analyses identified PRO-C3 (area under curve [AUC] = 0.87) as the ECM marker with the best diagnostic performance. The ECM biomarkers correlated with inflammation biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6] and YKL-40) but not with CA19-9. To investigate prognostic performance, patients were split into three cohorts (first-line, second-line and surgery). Elevated ECM biomarker levels were associated with short overall survival (OS), but only pretreatment PRO-C3 and PRO-C6 were associated with OS in both the first-line and second-line settings when adjusting for CA19-9, performance status and stage in a multivariate Cox-regression analyses. Our results indicate that collagen remodeling is increased in patients with BTC and associated with survival. The collagen pro-peptides (PRO-C3 and PRO-C6) could be used as novel biomarkers in these patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias do Sistema Biliar / Colágeno Tipo IV Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Int J Cancer Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Dinamarca

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias do Sistema Biliar / Colágeno Tipo IV Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Int J Cancer Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Dinamarca