Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers.
Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers.
复制标题
DOI：
10.1186/s12885-018-4242-8
复制
发表时间：
2018-03-27
期刊：
影响因子：
3.8
通讯作者：
Mes-Masson AM
中科院分区：
文献类型：
--
作者：
Le Page C;Rahimi K;Köbel M;Tonin PN;Meunier L;Portelance L;Bernard M;Nelson BH;Bernardini MQ;Bartlett JMS;Bachvarov D;Gotlieb WH;Gilks B;McAlpine JN;Nachtigal MW;Piché A;Watson PH;Vanderhyden B;Huntsman DG;Provencher DM;Mes-Masson AM
由于早期传播和对铂类化疗的获得性耐药，卵巢癌是最致命的妇科恶性肿瘤。需要独立且与临床参数互补的可靠标志物来改善对该疾病患者的管理。加拿大卵巢实验统一资源 (COEUR) 为研究人员提供生物材料和相关临床数据，以进行生物标志物验证研究。使用加拿大组织存储库网络 (CTRNet) 定义的标准，我们之前已经证明了来自该资源的生物材料的质量。在这里，我们描述了 COEUR 队列的临床特征。在加拿大 12 个卵巢癌生物库的支持下，我们创建了一个中央回顾性队列，由 2000 多个患者组织样本和相关临床数据组成，其中包括 1246 个高级别浆液性癌、102 个低级别浆液性癌、295 个子宫内膜样癌、259 个透明细胞癌和 89 个粘液性癌组织型。应用两步重分类过程来确保当代组织学分类（组织分型）。对于每种组织型，我们通过 Kaplan-Meier 和 Cox 比例风险回归分析评估了已知的临床病理参数（分期、细胞减灭术、化疗、BRCA1 和 BRCA2 突变）与患者结果之间的关联。该队列的中位随访时间为 45 个月，高级别浆液性癌患者的 5 年生存率为 34%，而子宫内膜样癌患者的 5 年生存率为 80%。当按阶段或细胞减灭术分层时，生存概况因组织型而异。患有晚期粘液癌或透明细胞癌或患有非最佳减瘤疾病的女性预后最差。在高级别浆液性癌中，我们观察到，与没有可检测到的突变的患者相比，携带 BRCA1 或 BRCA2 突变的女性与更长的生存期显着相关。我们的结果显示了与当前文献相比，每种组织型的预期生存率，表明该队列是五种主要组织型的公正代表。 COEUR是一站式综合生物样本库，全面收集成熟的结果数据和相关临床数据，可进行分层分析。
Ovarian carcinoma is the most lethal gynecological malignancy due to early dissemination and acquired resistance to platinum-based chemotherapy. Reliable markers that are independent and complementary to clinical parameters are needed to improve the management of patients with this disease. The Canadian Ovarian Experimental Unified Resource (COEUR) provides researchers with biological material and associated clinical data to conduct biomarker validation studies. Using standards defined by the Canadian Tissue Repository Network (CTRNet), we have previously demonstrated the quality of the biological material from this resource. Here we describe the clinical characteristics of the COEUR cohort. With support from 12 Canadian ovarian cancer biobanks in Canada, we created a central retrospective cohort comprised of more than 2000 patient tissue samples with associated clinical data, including 1246 high-grade serous, 102 low-grade serous, 295 endometrioid, 259 clear cell and 89 mucinous carcinoma histotypes. A two-step reclassification process was applied to assure contemporary histological classification (histotyping). For each histotypes individually, we evaluated the association between the known clinico-pathological parameters (stage, cytoreduction, chemotherapy treatment, BRCA1 and BRCA2 mutation) and patient outcome by using Kaplan-Meier and Cox proportional hazard regression analyses. The median follow-up time of the cohort was 45 months and the 5-year survival rate for patients with high-grade serous carcinomas was 34%, in contrast to endometrioid carcinomas with 80% at 5 years. Survival profiles differed by histotype when stratified by stage or cytoreduction. Women with mucinous or clear cell carcinomas at advanced stage or with non-optimally debulked disease had the worst outcomes. In high-grade serous carcinoma, we observed significant association with longer survival in women harboring BRCA1 or BRCA2 mutation as compared to patients without detectable mutation. Our results show the expected survival rates, as compared with current literature, in each histotype suggesting that the cohort is an unbiased representation of the five major histotypes. COEUR, a one stop comprehensive biorepository, has collected mature outcome data and relevant clinical data in a comprehensive manner allowing stratified analysis.