Spentzos Dimitrios, Levine Douglas A, Ramoni Marco F, Joseph Marie, Gu Xuesong, Boyd Jeff, Libermann Towia A, Cannistra Stephen A
Program of Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
J Clin Oncol. 2004 Dec 1;22(23):4700-10. doi: 10.1200/JCO.2004.04.070. Epub 2004 Oct 25.
Currently available clinical and molecular prognostic factors provide an imperfect assessment of prognosis for patients with epithelial ovarian cancer (EOC). In this study, we investigated whether tumor transcription profiling could be used as a prognostic tool in this disease.
Tumor tissue from 68 patients was profiled with oligonucleotide microarrays. Samples were randomly split into training and validation sets. A three-step training procedure was used to discover a statistically significant Kaplan-Meier split in the training set. The resultant prognostic signature was then tested on an independent validation set for confirmation.
In the training set, a 115-gene signature referred to as the Ovarian Cancer Prognostic Profile (OCPP) was identified. When applied to the validation set, the OCPP distinguished between patients with unfavorable and favorable overall survival (median, 30 months v not yet reached, respectively; log-rank P = .004). The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. The hazard ratio for death in the unfavorable OCPP group was 4.8 (P = .021 by Cox proportional hazards analysis).
The OCPP is an independent prognostic determinant of outcome in EOC. The use of gene profiling may ultimately permit identification of EOC patients appropriate for investigational treatment approaches, based on a low likelihood of achieving prolonged survival with standard first-line platinum-based therapy.
目前可用的临床和分子预后因素对上皮性卵巢癌(EOC)患者预后的评估并不完善。在本研究中,我们调查了肿瘤转录谱分析是否可作为该疾病的一种预后工具。
用寡核苷酸微阵列对68例患者的肿瘤组织进行分析。样本被随机分为训练集和验证集。采用三步训练程序在训练集中发现具有统计学意义的Kaplan-Meier分割。然后在独立的验证集上测试所得的预后特征以进行确认。
在训练集中,鉴定出一个由115个基因组成的特征,称为卵巢癌预后谱(OCPP)。当应用于验证集时,OCPP区分了总生存期不佳和良好的患者(中位数分别为30个月和尚未达到;对数秩检验P = 0.004)。在多变量分析中,该特征保持独立的预后价值,同时控制其他已知的预后因素,如年龄、分期、分级和减瘤状态。OCPP不良组的死亡风险比为4.8(Cox比例风险分析,P = 0.021)。
OCPP是EOC患者预后的独立决定因素。基因谱分析的应用最终可能有助于识别那些基于标准一线铂类疗法延长生存期可能性低而适合采用试验性治疗方法的EOC患者。