Four-Gene Expression Ratio Test for Survival in Patients Undergoing Surgery for Mesothelioma
Four-Gene Expression Ratio Test for Survival in Patients Undergoing Surgery for Mesothelioma
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DOI：
10.1093/jnci/djp061
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发表时间：
2009-05-06
影响因子：
10.3
通讯作者：
Bueno, Raphael
中科院分区：
文献类型：
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作者：
Gordon, Gavin J.;Dong, Lingsheng;Bueno, Raphael
恶性胸膜间皮瘤有几个有效的治疗，一个是细胞减灭术。我们以前开发了一个基因比率测试，以预测恶性胸膜间皮瘤患者接受手术的结果。在这项研究中，我们调查了预测价值和技术检测性能的检测恶性胸膜间皮瘤患者的临床数据，获得了前瞻性的连续120例恶性胸膜间皮瘤谁预定在一个机构的减积手术。标本在手术或胸膜活检检查时获得。从肿瘤标本中收集四种基因的表达数据，并通过定量逆转录-聚合酶链反应确定三种基因表达比率（TM 4SF 1/PKM 2、TM 4SF 1/ARHGDIA和COBLL 1/ARHGDIA）。通过基因比率检验将患者分配到良好或不良结局组。在单变量分析中，通过Kaplan-Meier方法和对数秩检验估计生存期。多变量考克斯比例风险模型用于控制预后因素。通过使用每例患者最多30份标本、两种活检技术和两个性能部位来确定技术稳健性。所有统计检验均为双侧检验，单变量分析中该检验预测总生存期（P <0.001）和癌症特异性生存期（P = 0.007），多变量分析中预测总生存期（死亡风险比= 2.09，95%置信区间[CI] = 1.27 - 3.45，P = 0.004）。该试验在患者体内具有重现性，并且对于肿瘤细胞含量差异很大的标本，两次测定之间具有重复性。两次测定之间的重复性为88.5%（95% CI = 84.0%-92.2%），或当排除技术上不可接受的检测值时，为91.9%（95% CI = 87.4%-95.1%）。两次测定之间的重现性为96.1%（95% CI = 86.5%-99.5%）。结合基因比率检验和其他预后因素，可以前瞻性区分高危患者（中位生存期= 6.9个月，95% CI = 2.6至8.9个月; 3年生存率= 0%）和低风险（中位生存期= 31.9个月，95%CI = 21.9至41.7个月; 3年生存期= 42%）。恶性胸膜间皮瘤患者生存期的基因比率检验具有稳健的预测价值和技术测定性能。
Malignant pleural mesothelioma has few effective treatments, one being cytoreductive surgery. We previously developed a gene ratio test to predict outcome of malignant pleural mesothelioma patients undergoing surgery. In this study, we investigated the predictive value and technical assay performance of this test in patients with malignant pleural mesothelioma.Clinical data were obtained prospectively from 120 consecutive patients with malignant pleural mesothelioma who were scheduled for debulking surgery at one institution. Specimens were obtained at surgery or by pleural biopsy examination. Expression data for four genes were collected from tumor specimens, and three ratios of gene expression (TM4SF1/PKM2, TM4SF1/ARHGDIA, and COBLL1/ARHGDIA) were determined by quantitative reverse transcriptase-polymerase chain reaction. Patients were assigned to good or poor outcome groups by the gene ratio test. Survival was estimated by the Kaplan-Meier method and the log-rank test in univariate analyses. A multivariable Cox proportional hazards model was used to control for prognostic factors. Technical robustness was determined by using up to 30 specimens per patient, two biopsy techniques, and two performance sites. All statistical tests were two-sided.The test predicted overall survival (P < .001) and cancer-specific survival (P = .007) in univariate analysis and overall survival in multivariable analysis (hazard ratio for death = 2.09, 95% confidence interval [CI] = 1.27 to 3.45, P = .004). The test was reproducible within patients and repeatable between two determinations for specimens with widely varying tumor cell contents. Repeatability between two determinations was 88.5% (95% CI = 84.0% to 92.2%) or, when technically unacceptable test values were excluded, 91.9% (95% CI = 87.4% to 95.1%). Reproducibility between two determinations was 96.1% (95% CI = 86.5% to 99.5%). Combining the gene ratio test and other prognostic factors allowed prospective discrimination between patients at high risk (median survival = 6.9 months, 95% CI = 2.6 to 8.9 months; 3-year survival = 0%) and low risk (median survival = 31.9 months, 95% CI = 21.9 to 41.7 months; 3-year survival = 42%).The gene ratio test for survival of patients with malignant pleural mesothelioma has robust predictive value and technical assay performance.