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

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
• cervical cancer
• CHI3L1
• prognosis
• YKL-40

Acknowledgments

We thank Tonni Løve Hansen, Ulla Kjaerulff-Hansen, and Inge Hald, Herlev Hospital for excellent technical assistance. The patients are thanked for their willingness to participate.

Author contributions

Study design: all authors; Administrative support: all authors; Provision of study materials or patients: CP, HJN and BJM; Collection and assembly of data: all authors; Data analysis and interpretation: AR, JSJ, IJC and BJM; Manuscript writing: AR, JSJ, IJC and BJM; and Final approval of manuscript: all authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Quidel had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. The authors had full access to all the data in the study and had the final responsibility for the decision to submit the manuscript for publication.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

The present work was financially supported by Quidel, who also provided the study with YKL-40 ELISA kits.