Serum kynurenine levels are a novel biomarker to predict the prognosis of patients with hepatocellular carcinoma

PLoS One. 2020 Oct 21;15(10):e0241002. doi: 10.1371/journal.pone.0241002. eCollection 2020.

Abstract

Background: We examined serum kynurenine levels in patients with chronic hepatitis C virus infection, and the relationship between serum kynurenine and prognosis in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C.

Methods: We retrospectively analyzed 604 patients with HCC diagnosed between January 1999 and December 2015, and 288 patients without HCC who were seen at the National Hospital Organization Nagasaki Medical Center between October 2014 and November 2017. The association between serum kynurenine and prognosis was evaluated using the Cox's proportional hazards regression analysis.

Results: Patients with HCC had significantly higher values of serum kynurenine than patients without HCC (median: 557.1 vs. 464.2 ng/mL, p<0.001). Five-year survival rates of HCC patients with serum kynurenine ≥900 (n = 65), 600-899 (n = 194), and <600 ng/mL (n = 345) were 30.6%, 47.4%, and 61.4%, respectively (p = 0.001, log-rank test). Multivariate analysis identified serum kynurenine as an independent predictor for prognosis of HCC patients. The hazard ratio of serum kynurenine ≥900, and 600-899 compared with serum kynurenine <600 ng/mL were 1.91 (p<0.001) and 1.37 (p = 0.015), respectively.

Conclusions: A high level of serum kynurenine correlated with poor prognosis of HCC. Serum kynurenine levels may be a novel biomarker to predict the prognosis of patients with HCC. The development of drugs that inhibit kynurenine production is expected to help improve the prognosis of patients with HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Humans
  • Kaplan-Meier Estimate
  • Kynurenine / blood*
  • Liver Neoplasms / blood
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Kynurenine

Grants and funding

This research was supported by Japan Agency for Medical Research and Development under Grant Number JP19fk0210019. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.