Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Mol Pharm. 2011 Dec 5;8(6):2080-8. doi: 10.1021/mp200240a. Epub 2011 Jul 15.
The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art TaqMan-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment [complete response (CR) vs other], and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS, log-rank p = 0.0000; and PFS, log-rank p = 0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions.
浆膜腔积液中肿瘤细胞的存在是晚期癌症的临床表现，通常与预后不良相关。鉴定分子靶点可能有助于设计有效的治疗方法来根除这些侵袭性癌细胞，从而提高患者的生存率。我们使用最先进的 TaqMan 基于 qRT-PCR 的检测方法，研究了 32 例未经配对的卵巢浆液性癌积液样本的多药耐药 (MDR) 转录组，这些样本是在诊断时或化疗后疾病复发时获得的。MDR 基因是根据过去三十年发表的文献进行广泛的整理后预先选择的。我们发现了三个与总生存期 (OS)、治疗反应 [完全缓解 (CR) 与其他] 和无进展生存期 (PFS) 具有统计学显著相关性的基因特征。特征的中位数对数秩 p 值分别为 0.023、0.034 和 0.008。与细胞减灭术后残余肿瘤状态、根据国际妇产科联合会定义的治疗 (是否联合化疗) 和分期均无相关性。进一步的分析表明，基因表达本身可以有效地预测卵巢浆液性癌患者的生存结局（OS，对数秩 p = 0.0000；PFS，对数秩 p = 0.002）。有趣的是，总生存的特征在初次就诊和接受化疗后复发的患者中是相同的。这项初步研究强调了两个新的基因特征，它们可能有助于优化卵巢癌患者的治疗。
