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.

摘要

炎症是癌症的标志之一，在癌症的发展和进展中起着至关重要的作用。本研究的目的是调查高血清 YKL-40 是否与宫颈癌 (CC) 患者的不良预后有关。一项针对 116 名 CC 患者的前瞻性生物标志物研究（FIGO Ia 期：n  = 4；Ib：n  = 55；II：n  = 26；III：n  = 26；IV：n = 5) 和 152 名宫颈上皮内瘤变 (CIN) 患者。患者在 2001-2004 年期间根据标准指南接受了初次手术、放疗和化疗。70 名患者在随访期间死亡（中位数 117 个月，范围 104-131）。YKL-40的血清浓度通过ELISA测量。YKL-40 的血清浓度增加（p < .001) 在 CC 患者（中位数 76 µg/L，IQR 45-148）中与 CIN 患者（44 µg/L，IQR 30-61）和健康女性（41 µg/L，IQR 29-58）相比。30 名 (26%) 的 CC 患者的 YKL-40 升高（> 健康女性中 YKL-40 的年龄校正第 95 个百分位数）。单变量 Cox 分析表明 YKL-40（作为对数转换的连续变量（基数 2）包括在内）与无复发生存期 (RFS) 相关（HR = 1.48，95% CI：1.11–1.98，p  = .008 ）和总生存期 (OS)（HR = 1.74, 1.44–2.10, p  < .0001）。多变量 Cox 分析显示阶段（II + III 与 I：HR = 2.92、1.37-6.20，p  = .005）、YKL-40（HR = 1.35、1.06-1.73，p  = .018 ）和年龄（HR = 1.56, 1.21–1.99, p = .0005) 是 OS 的独立预后变量。在治疗期间，与基线水平相比，YKL-40 增加 2 倍与较短的 RFS（HR = 1.87、1.27–2.77，p  = .0016）和 OS（HR = 1.78、1.26–2.50，p  = .0010）相关）。血清 YKL-40 是宫颈癌患者 OS 的独立生物标志物。