Clinical Relevance of Multidrug Resistance Gene Expression in Ovarian Serous Carcinoma Effusions
Clinical Relevance of Multidrug Resistance Gene Expression in Ovarian Serous Carcinoma Effusions
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DOI：
10.1021/mp200240a
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发表时间：
2011-11-01
影响因子：
4.9
通讯作者：
Gottesman, Michael M.
中科院分区：
文献类型：
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作者：
Gillett, Jean-Pierre;Wang, Junbai;Gottesman, Michael M.
浆膜腔积液中存在肿瘤细胞是晚期癌症的临床表现，通常与生存率低相关。确定分子靶点可能有助于设计有效的治疗方法，以根除这些侵袭性癌细胞并提高患者的生存率。使用最先进的基于TaqMan的qRT-PCR检测方法，我们研究了32例诊断或化疗后疾病复发时获得的未配对卵巢浆液性癌积液样本的多药耐药（MDR）转录组。MDR基因的选择是基于对过去三十年中发表的文献的广泛整理。我们发现三个基因特征与总生存期（OS）、治疗反应[完全缓解（CR）vs其他]和无进展生存期（IFS）具有统计学显著相关性。特征的中位对数秩p值分别为0.023、0.034和0.008。根据国际妇产科联合会的定义，未发现与肿瘤细胞减灭术后残留肿瘤状态、治疗（有或无化疗）和分期相关。进一步的分析表明，单独的基因表达可以有效地预测卵巢浆液性癌患者的生存结果（OS，对数秩p = 0.0000; PFS，对数秩p = 0.002）。有趣的是，总生存率的标志在首次出现的患者和那些接受化疗和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，可能有助于优化卵巢癌患者的治疗。
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 (IFS). 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.