Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases

PLoS One. 2020 Aug 5;15(8):e0236569. doi: 10.1371/journal.pone.0236569. eCollection 2020.

Abstract

Background: The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases.

Methods: Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis.

Results: Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33).

Conclusion: The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Tumor-Associated, Carbohydrate / blood
  • Biomarkers, Tumor / blood*
  • Carcinoembryonic Antigen / blood
  • Chitinase-3-Like Protein 1 / blood
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Female
  • Hepatectomy
  • Humans
  • Interleukin-6 / blood
  • Liver Neoplasms / blood*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Prognosis
  • Progression-Free Survival

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Biomarkers, Tumor
  • CHI3L1 protein, human
  • Carcinoembryonic Antigen
  • Chitinase-3-Like Protein 1
  • Interleukin-6
  • carbohydrate antigen 199, human

Grants and funding

This study was financially supported by the Competitive State Research Financing of the Expert Responsibility Area of Helsinki University Hospital (RP, PO, HI) and Tampere University Hospital (PO), the Cancer Foundation Finland (RP, PO, HI), Suomen Onkologiayhdistys (RP), the Danish Cancer Society (MG), and Finska Läkaresällskapet (PO). The YKL-40 and IL-6 kits and analysis were funded by the Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.