前列腺癌是一种十分复杂的癌症，变化多端，有的患者可以活很长时间，而有的患者却很快地死去。因此，开发出有效的检测手段来评定不同类型的病症十分重要。英国癌症研究所最新发布的新闻公报称，该所科学家最近开发出一种新的血液检测手段，可利用基因活动的特点快速检测出前列腺癌症患者病情的严重程度。研究人员相信，这一血检手段可最终与现在的PSA（前列腺特异性抗原）测试并用，用来判定哪些患者需要立即进行治疗。
在最近一期的《柳叶刀·肿瘤学》杂志上，英国癌症研究所的研究人员阐释了他们的研究成果。他们对英国100名前列腺癌症患者血液样本中的基因进行了扫描，这些患者中有69人病情已进入晚期，另外的31人则属于早期癌症患者。利用统计模型，研究人员将病人分成四组，每一组人员的基因活动方式皆不相同。在对患者长达两年半的病情进行系统评估之后，研究人员发现，其中一组患者的存活几率明显低于其他患者。而进一步分析发现，在这组患者中，每名患者身上都有9个关键基因异常活跃。通过与美国的70名前列腺癌症患者的样本进行对比后，研究人员确认，通过这9个基因的活动模式可以准确确认哪些患者的生存几率更小。数据表明，具有这种基因活动模式的患者的平均存活时间为9.2个月，而其他患者的平均存活时间则为21.6个月。
研究人员表示，对于癌症治疗来说，个性化治疗是未来的方向。最新的研究表明，通过病人的基因活动模式可以判定病患肿瘤的恶性程度，这种基因活动模式就如条形码，可快速简便地加以识别。而这种通过读取前列腺患者基因变化情况来判定癌症病情的血检手段则是一个重要的进展，可以使得医生能够更好地对病患进行针对性治疗。
Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study
Background Biomarkers are urgently needed to dissect the heterogeneity of prostate cancer between patients to improve treatment and accelerate drug development. We analysed blood mRNA expression arrays to identify patients with metastatic castration-resistant prostate cancer with poorer outcome.
Methods Whole blood was collected into PAXgene tubes from patients with castration-resistant prostate cancer and patients with prostate cancer selected for active surveillance. In stage I (derivation set), patients with castration-resistant prostate cancer were used as cases and patients under active surveillance were used as controls. These patients were recruited from The Royal Marsden Hospital NHS Foundation Trust (Sutton, UK) and The Beatson West of Scotland Cancer Centre (Glasgow, UK). In stage II (validation-set), patients with castration-resistant prostate cancer recruited from the Memorial Sloan-Kettering Cancer Center (New York, USA) were assessed. Whole-blood RNA was hybridised to Affymetrix U133plus2 microarrays. Expression profiles were analysed with Bayesian latent process decomposition (LPD) to identify RNA expression profiles associated with castration-resistant prostate cancer subgroups; these profiles were then confirmed by quantative reverse transcriptase (qRT) PCR studies and correlated with overall survival in both the test-set and validation-set.
Findings LPD analyses of the mRNA expression data divided the evaluable patients in stage I (n=94) into four groups. All patients in LPD1 (14 of 14) and most in LPD2 (17 of 18) had castration-resistant prostate cancer. Patients with castration-resistant prostate cancer and those under active surveillance comprised LPD3 (15 of 31 castration-resistant prostate cancer) and LDP4 (12 of 21 castration-resistant prostate cancer). Patients with castration-resistant prostate cancer in the LPD1 subgroup had features associated with worse prognosis and poorer overall survival than patients with castration-resistant prostate cancer in other LPD subgroups (LPD1 overall survival 10·7 months [95% CI 4·1—17·2] vs non-LPD1 25·6 months [18·0—33·4]; p<0·0001). A nine-gene signature verified by qRT-PCR classified patients into this LPD1 subgroup with a very low percentage of misclassification (1·2%). The ten patients who were initially unclassifiable by the LPD analyses were subclassified by this signature. We confirmed the prognostic utility of this nine-gene signature in the validation castration-resistant prostate cancer cohort, where LPD1 membership was also associated with worse overall survival (LPD1 9·2 months [95% CI 2·1—16·4] vs non-LPD1 21·6 months [7·5—35·6]; p=0·001), and remained an independent prognostic factor in multivariable analyses for both cohorts.
文献链接：https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70372-8/abstract
