Chiang Ying-Cheng, Lin Han-Wei, Chang Chi-Fang, Chang Ming-Cheng, Fu Chi-Feng, Chen Tsung-Ching, Hsieh Shu-Feng, Chen Chi-An, Cheng Wen-Fang
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Oncotarget. 2015 Nov 24;6(37):39740-55. doi: 10.18632/oncotarget.5469.
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.
我们提出将几丁质酶3样蛋白1(CHI3L1)作为上皮性卵巢癌(EOC)患者的预后生物标志物,并指出CHI3L1可能的生物学功能。我们采用定量实时聚合酶链反应(qRT-PCR)检测了180例EOC女性患者的CHI3L1表达,并评估CHI3L1表达、临床病理特征与患者预后之间的相关性。CHI3L1在癌组织中的表达高于正常组织。CHI3L1在浆液性组织学类型、晚期和化疗耐药患者中的表达也更高。CHI3L1高表达的患者无进展生存期较短(p < 0.001),总生存期也较短(p < 0.001)。CHI3L1高表达的患者复发风险(p < 0.001)和死亡风险也较高(p < 0.001)。体外研究表明,CHI3L1上调抗凋亡Mcl-1蛋白的表达,并阻碍紫杉醇诱导的卵巢癌细胞凋亡。这些结果表明,CHI3L1有望成为EOC的预后生物标志物。CHI3L1可能通过上调Mcl-1抑制药物诱导的凋亡来促进化疗耐药。