Prognostic utility of serum YKL-40 in patients with cervical cancer

Scand J Clin Lab Invest. 2020 Dec;80(8):687-693. doi: 10.1080/00365513.2020.1846209. Epub 2020 Nov 13.

Abstract

Inflammation is one of the hallmarks of cancer and plays a crucial role in the development and progression. The objective of the present study was to investigate if high serum YKL-40 is related to poor prognosis in cervical cancer (CC) patients. A prospective biomarker study of 116 patients with CC (FIGO stage Ia: n = 4; Ib: n = 55; II: n = 26; III: n = 26; IV: n = 5) and 152 patients with cervical intraepithelial neoplasia (CIN). The patients received primary surgery, radiotherapy and chemotherapy according to standard guidelines during the period 2001-2004. Seventy patients died during the follow-up period (median 117 months, range 104-131). Serum concentrations of YKL-40 were measured by ELISA. Serum concentrations of YKL-40 were increased (p < .001) in CC patients (median 76 µg/L, IQR 45-148) compared to CIN patients (44 µg/L, IQR 30-61) and healthy women (41 µg/L, IQR 29-58). YKL-40 was elevated (>age-corrected 95th percentile of YKL-40 in healthy women) in 30 (26%) of the CC patients. Univariate Cox analysis demonstrated that YKL-40 (included as a log-transformed continuous variable (base 2)) was associated with recurrence-free survival (RFS) (HR = 1.48, 95% CI: 1.11-1.98, p = .008) and overall survival (OS) (HR = 1.74, 1.44-2.10, p < .0001). Multivariate Cox analysis showed that stage (II + III vs. I: HR = 2.92, 1.37-6.20, p = .005), YKL-40 (HR = 1.35, 1.06-1.73, p = .018) and age (HR = 1.56, 1.21-1.99, p = .0005) were independent prognostic variables of OS. During treatment, a 2-fold increase in YKL-40 compared to baseline level was associated with short RFS (HR = 1.87, 1.27-2.77, p = .0016) and OS (HR = 1.78, 1.26-2.50, p = .0010). Serum YKL-40 is an independent biomarker of OS in patients with cervical cancer.

Keywords: Biomarkers; CHI3L1; YKL-40; cervical cancer; prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Chitinase-3-Like Protein 1 / blood
  • Chitinase-3-Like Protein 1 / genetics*
  • Diagnosis, Differential
  • Female
  • Gene Expression
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Uterine Cervical Dysplasia / blood
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / mortality
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1