Abstract
We propose CHI3L1 as a prognostic biomarker for patients with epithelial ovarian carcinoma (EOC) and also suggest possible biological functions of CHI3L1. We measured CHI3L1 expression with quantitative real time-polymerase chain reaction (qRT-PCR) in 180 women with EOC and evaluated correlations between CHI3L1 expression, clinicopathological characteristics, and the outcomes of the patients. The expression of CHI3L1 was higher in cancerous tissues than in normal tissues. The expression of CHI3L1 was also higher in patients with a serous histological type, advanced stage, and chemoresistance. Patients with high CHI3L1 expression had a shorter progression-free survival (p < 0.001)and overall survival (p < 0.001). Patients with high CHI3L1 expression also had a high risk of recurrence (p < 0.001)and death (p < 0.001). In vitro studies showed that CHI3L1 up-regulated the expression of anti-apoptotic Mcl-1 protein and hampered paclitaxel-induced apoptosis of ovarian cancer cells. These results suggest that CHI3L1 shows potential as a prognostic biomarker for EOC. CHI3L1 may promote chemoresistance via inhibition of drug-induced apoptosis by up-regulating Mcl-1.
Highlights
Epithelial ovarian carcinoma (EOC) has received increasing attention in recent years because it is associated with the highest mortality rate among gynecologic malignancies [1, 2]
The expression of Chitinase 3-like 1 (CHI3L1) is higher in patients with EOC that present with a serous histologic type, advanced stage, chemoresistance, and poor outcome
We found that CHI3L1 expression in cancerous tissues is a prognostic biomarker for patients with EOC
Summary
Epithelial ovarian carcinoma (EOC) has received increasing attention in recent years because it is associated with the highest mortality rate among gynecologic malignancies [1, 2]. Current management strategies include debulking surgery and adjuvant chemotherapy with a regimen of platinum and paclitaxel, which has a response rate of 80% for all patients and 40–60% for advanced-stage patients [4]. Patients, especially those with an advanced stage, usually relapse after an initial response and die of recurrence [3]. Chemoresistance is an obstacle in the management of ovarian cancer To overcome this problem several mechanisms have been proposed including suppression of apoptotic pathways, increased DNA repair and over-expression of multidrugresistance genes [5,6,7]. Elucidating the mechanisms of chemoresistance may be helpful in the development of new therapeutic strategies
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