Academic Oncology, University of Nottingham, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, Nottingham, UK.
J Cell Mol Med. 2012 Oct;16(10):2422-8. doi: 10.1111/j.1582-4934.2012.01559.x.
Ovarian cancer is routinely treated with surgery and platinum-based chemotherapy. Resistance is a major obstacle in the efficacy of this chemotherapy regimen and the ability to identify those patients at risk of developing resistance is of considerable clinical importance. The expression of calpain-1, calpain-2 and calpastatin were determined using standard immunohistochemistry on a tissue microarray of 154 primary ovarian carcinomas from patients subsequently treated with platinum-based adjuvant chemotherapy. High levels of calpain-2 expression was significantly associated with platinum resistant tumours (P = 0.031). Furthermore, high expression of calpain-2 was significantly associated with progression-free (P = 0.049) and overall survival (P = 0.006) in this cohort. The association between calpain-2 expression and overall survival remained significant in multivariate analysis accounting for tumour grade, stage, optimal debulking and platinum sensitivity (hazard ratio = 2.174; 95% confidence interval = 1.144-4.130; P = 0.018). The results suggest that determining calpain-2 expression in ovarian carcinomas may allow prognostic stratification of patients treated with surgery and platinum-based chemotherapy. The findings of this study warrant validation in a larger clinical cohort.
卵巢癌的常规治疗方法是手术和铂类化疗。耐药性是该化疗方案疗效的主要障碍,能够识别那些有耐药风险的患者具有重要的临床意义。在接受铂类辅助化疗的 154 例原发性卵巢癌患者的组织微阵列上,使用标准免疫组织化学方法测定钙蛋白酶-1、钙蛋白酶-2 和钙蛋白酶抑制剂的表达。钙蛋白酶-2 表达水平高与铂类耐药肿瘤显著相关(P=0.031)。此外,在该队列中,钙蛋白酶-2 的高表达与无进展生存期(P=0.049)和总生存期(P=0.006)显著相关。在多变量分析中,考虑到肿瘤分级、分期、最佳减瘤术和铂类敏感性后,钙蛋白酶-2 表达与总生存期之间的关联仍然显著(风险比=2.174;95%置信区间=1.144-4.130;P=0.018)。这些结果表明,在卵巢癌中测定钙蛋白酶-2 的表达可能允许对接受手术和铂类化疗的患者进行预后分层。本研究的结果需要在更大的临床队列中进行验证。