诊断时活检样本中的恶性场特征分析鉴定了患有局限性Gleason 6和7前列腺癌的患者的致命疾病
Malignant field signature analysis in biopsy samples at diagnosis identifies lethal disease in patients with localized Gleason 6 and 7 prostate cancer
摘要：
早期低风险前列腺癌（PC）患者的过度治疗是疾病管理中的一个重要问题，并具有社会经济影响。在诊断为低度局限性PC的患者中开发具有临床意义的疾病的遗传和分子标志物将对疾病管理产生重大影响。在瑞典随访长达30年的观察等待队列中，在诊断时从Gleason 6和Gleason 7肿瘤患者获得的活检标本中报告了致死性PC的基因表达特征（GES）。在G7和G6患者中，98个基因的GES分别确定了诊断后4年所有死亡事件的89%和100%;在6年随访时，捕获了所有死亡事件的83%和100%。值得注意的是，98个基因的GES似乎在样本中只有2%的癌细胞分层的患者中成功地执行，强烈表明它捕获了具有不同程度侵袭性的癌细胞的前列腺中的恶性场效应。在65岁或以下PC患者的G6和G7肿瘤中，GES在整个随访期间发现了86%的死亡事件。在70岁或更年轻的PC患者的G6和G7肿瘤中，GES确定了诊断后6年所有死亡事件的90%。本研究中报告的致死性PC的98个基因GES的分类性能似乎适合于满足前瞻性4至6年临床试验的设计和可行性要求，这对于临床环境中的诊断和预后测试的监管批准至关重要。在G6和G7肿瘤活检标本中，经验证的GES将有助于医生在诊断时识别应考虑从主动监测计划中排除的患者，以及最有可能从立即治疗干预中获益的患者。
英文摘要：
Overtreatment of early-stage low-risk prostate cancer (PC) patients represents a significant problem in disease management and has socio-economic implications. Development of genetic and molecular markers of clinically significant disease in patients diagnosed with low grade localized PC would have a major impact in disease management. A gene expression signature (GES) is reported for lethal PC in biopsy specimens obtained at the time of diagnosis from patients with Gleason 6 and Gleason 7 tumors in a Swedish watchful waiting cohort with up to 30 years follow-up. A 98-genes GES identified 89 and 100 percent of all death events 4 years after diagnosis in G7 and G6 patients, respectively; at 6 years follow-up, 83 and 100 percent of all deaths events were captured. Remarkably, the 98-genes GES appears to perform successfully in patients stratification with as little as 2% of cancer cells in a specimen, strongly indicating that it captures a malignant field effect in prostates harboring cancer cells of different degrees of aggressiveness. In G6 and G7 tumors from PC patients of age 65 or younger, GES identified 86 percent of all death events during the entire follow-up period. In G6 and G7 tumors from PC patients of age 70 or younger, GES identified 90 percent of all death events 6 years after diagnosis. Classification performance of the reported in this study 98-genes GES of lethal PC appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial, which is essential for regulatory approval of diagnostic and prognostic tests in clinical setting. Prospectively validated GES of lethal PC in biopsy specimens of G6 and G7 tumors will help physicians to identify, at the time of diagnosis, patients who should be considered for exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions.
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