Department of Oncology, Karolinska University Hospital, Sweden.
Int J Gynecol Cancer. 2013 Mar;23(3):448-55. doi: 10.1097/IGC.0b013e318284308b.
Heat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.
Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher's exact test. Median follow-up was 60 months.
High HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3-8.5) and PFI (HR, 3.3; 95% CI, 1.5-7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5-7.1) and PFI (HR, 2.6; 95% CI, 1.3-5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.
Heat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.
热休克蛋白 60(HSP60)在恶性细胞存活中发挥重要作用。我们评估了 HSP60 在晚期卵巢癌中的预后和治疗预测价值。
前瞻性地从 123 名接受疑似晚期卵巢癌初次手术的患者中采集新鲜肿瘤样本。其中 57 名患者符合纳入标准,即国际妇产科联合会(FIGO)分期 IIIC-IV 期、浆液性/子宫内膜样肿瘤、铂类化疗和肿瘤细胞占比 50%或以上的标本。采用实时聚合酶链反应和免疫组织化学法检测 HSP60 mRNA 和蛋白表达。采用 Cox 比例风险模型估计 HSP60 与总生存期(OS)和无铂间期(PFI)的相关性,并采用 Fisher 确切检验分析其与治疗反应的关系。中位随访时间为 60 个月。
HSP60 mRNA 高表达与较短的 OS(风险比 [HR],3.4;95%置信区间 [CI],1.3-8.5)和 PFI(HR,3.3;95%CI,1.5-7.2)相关。同样,HSP60 蛋白高表达与较短的 OS(HR,3.2;95%CI,1.5-7.1)和 PFI(HR,2.6;95%CI,1.3-5.3)相关。HSP60 蛋白高表达患者的中位生存时间为 31 个月,而低表达患者的中位生存时间为 55 个月(P=0.016)。在 3 级浆液性肿瘤亚组中,OS 和 PFI 的影响更为显著。所有 HSP60 水平较低的患者对一线化疗均有反应。
HSP60 可能确定不同预后和治疗反应的高级别浆液性卵巢癌亚群。