Abstract
Numerous studies have investigated the prognostic role of YKL-40 in breast cancer, but yielded inconsistent results. To derive a more precise evaluation, relevant publications assessing the association between YKL-40 expression and clinical outcome of breast cancer patients were electronically searched and identified. A combined analysis of included studies was performed using fixed- or random-effect model to calculate the pooled hazard ratio (HR) or odds ratio(OR) and 95% confidence interval (95%CI) for the assessment of the association. Ten eligible studies involving 1250 patients were ultimately included in the meta-analysis. Overall, the pooled analysis showed that elevated YKL-40 expression was significantly associated with a poor overall survival(OS: HR=1.48, 95%CI= 1.11-1.97) and disease-free survival(DFS: HR=1.51, 95%CI= 1.10-2.07). The subgroup analysis by detection methods revealed an unfavorable OS in breast cancer patients with elevated YKL-40 expression evaluated by IHC(HR=1.39, 95%CI=1.12-1.71) but not by ELISA/RIA. Also, the stratification analysis by ethnicity showed a significant association between increased YKL-40 expression and shorter OS of breast cancer patients in western population(HR=1.51, 95%CI=1.03-2.21) as well as Asian population (HR=1.40, 95%CI= 1.05-1.86). Similarly, the subgroup analysis by detection methods revealed a significantly inferior DFS in breast cancer patients with increased YKL-40 expression disregarding the use of IHC(HR=2.02, 95%CI=1.47-2.79) or ELISA/RIA(HR=1.06, 95%CI= 1.02 -1.10). Additionally, increased YKL-40 expression was found to significantly correlate with larger tumor size (OR=2.38, 95%CI=1.41-4.05).The present meta-analysis indicate that elevated YKL-40 expression is associated with a poor prognosis in breast cancer patients. YKL-40 may serve as a promising predictive biomarker of prognosis of breast cancer.
Highlights
Breast cancer remains the most frequently diagnosed cancer among women worldwide and accounts globally for the leading cause of cancer death in females, taking up 29% of all new cancer cases and 14% of all cancer deaths [1, 2]
It is reported that serum levels of YKL-40 in patients with glioma are related with tumor grade and burden [14], and high YKL-40 expression is associated with poor survival of patients with lung cancer, glioblastoma, colorectal cancer, hepatocellular carcinoma, gastric cancer [15,16,17,18], supporting the notion that elevated YKL-40 expression may serve as a useful potential biomarker of prognosis for cancer patients
Of the ten included articles, adjusted multivariate analyses for the association between YKL-40 expression and the survival outcome of breast cancer patients were conducted in six publications, while unadjusted univariate analyses for this association were performed in four publications
Summary
Breast cancer remains the most frequently diagnosed cancer among women worldwide and accounts globally for the leading cause of cancer death in females, taking up 29% of all new cancer cases and 14% of all cancer deaths [1, 2]. In addition to the roles mentioned above, inhibition of YKL-40 was found to be able to attenuate the tube formation of microvascular endothelial cells in vitro and suppresse tumor growth, angiogenesis, and progression of brain tumors [11]. Such biophysiological activities were observed in several other malignancies [12], suggesting its angiogenic properties in cancer development. It is reported that serum levels of YKL-40 in patients with glioma are related with tumor grade and burden [14], and high YKL-40 expression is associated with poor survival of patients with lung cancer, glioblastoma, colorectal cancer, hepatocellular carcinoma, gastric cancer [15,16,17,18], supporting the notion that elevated YKL-40 expression may serve as a useful potential biomarker of prognosis for cancer patients
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