Most men with prostate cancer (PCa), despite potentially curable localized disease at initial diagnosis, progress to metastatic disease. Despite numerous treatment options, choosing the optimal treatment for individual patients remains challenging. Biomarkers guiding treatment sequences in an advanced setting are lacking. To estimate the diagnostic potential of liquid biopsies in guiding personalized treatment of PCa, we evaluated the utility of a custom-targeted next-generation sequencing (NGS) panel based on the AmpliSeq HD Technology. Ultra-deep sequencing on plasma circulating free DNA (cfDNA) samples of 40 metastatic castration-resistant PCa (mCRPC) and 28 metastatic hormone-naive PCa (mCSPC) was performed. CfDNA somatic mutations were detected in 48/68 (71%) patients. Of those 68 patients, 42 had matched tumor and cfDNA samples. In 21/42 (50%) patients, mutations from the primary tumor tissue were detected in the plasma cfDNA. In 7/42 (17%) patients, mutations found in the primary tumor were not detected in the cfDNA. Mutations from primary tumors were detected in all tested mCRPC patients (17/17), but only in 4/11 with mCSPC. AR amplifications were detected in 12/39 (31%) mCRPC patients. These results indicate that our targeted NGS approach has high sensitivity and specificity for detecting clinically relevant mutations in PCa.
尽管大多数前列腺癌患者在初次诊断时可能患有可治愈的局限性病变，但最终仍会进展为转移性疾病。尽管存在多种治疗方案，为个体患者选择最佳治疗策略仍具挑战性，目前尚缺乏能够指导晚期前列腺癌序贯治疗的生物标志物。为评估液体活检在前列腺癌个体化治疗中的诊断潜力，我们基于AmpliSeq HD技术开发了定制靶向二代测序（NGS）检测体系。通过对40例转移性去势抵抗性前列腺癌（mCRPC）和28例转移性激素敏感性前列腺癌（mCSPC）患者的血浆游离DNA（cfDNA）样本进行超深度测序，在68例患者中有48例（71%）检测到cfDNA体细胞突变。其中42例患者同时具备匹配的肿瘤组织和cfDNA样本，在21例（50%）患者血浆cfDNA中检测到与原发肿瘤组织一致的突变，另有7例（17%）患者原发肿瘤突变未在cfDNA中检出。值得注意的是，所有接受检测的mCRPC患者（17/17）均能在cfDNA中检出原发肿瘤突变，而mCSPC患者中仅4/11例（36%）呈现此特征。此外，在39例mCRPC患者中有12例（31%）检测到雄激素受体（AR）基因扩增。这些结果表明，我们建立的靶向NGS检测方法在前列腺癌临床相关突变检测中具有较高的敏感性和特异性。
Cell-Free DNA Genomic Profiling and Its Clinical Implementation in Advanced Prostate Cancer
肿瘤(癌症)患者之家