不同内脏转移性前列腺癌的临床基因组学研究

Genomic characterization of different visceral metastatic patterns in prostate cancer patients

目的揭示不同内脏转移模式的前列腺癌患者临床特征与基因组突变模式的差异。方法通过对复旦大学附属肿瘤医院前列腺癌前瞻性临床基因组队列中的859例患者进行分析,本研究筛选出75例内脏转移患者,其中肺转移41例,肝转移34例。所有患者均有统一完善的临床及基因组学信息。本研究对肺转移与肝转移两类转移模式与前列腺癌患者发病年龄、病理特征、疾病侵袭性等临床特征,以及重要驱动基因变异之间的关联进行了统计学分析。结果肺转移和肝转移在转移性去势敏感性前列腺癌中的发生率分别为9.3%和3.0%,转移性去势抵抗性前列腺癌的发生率分别为6.2%和9.1%。肺转移和肝转移前列腺癌在发病年龄、前列腺特异性抗原水平、Gleason评分等临床特征上并无显著性差异。但在基因层面,肝转移患者表现出更高的AR(38.2%vs 12.2%,P=0.013)和CCND1(20.6%vs 2.4%,P=0.02)拷贝数扩增频率、PTEN(20.6%vs 2.4%,P=0.02)和BRCA2(11.8%vs 0%,P=0.04)拷贝数缺失频率。结论转移性去势敏感期患者应重视肺转移的筛查,而对于去势抵抗期患者更应该警惕肝转移发生的可能。尽管当前不同内脏转移前列腺癌患者适用同一套治疗策略与标准,但关键驱动基因的差异提示肺转移与肝转移患者应该分而治之,以实现患者最大化生存获益。

Objective To explore the clinical and genomic characterization of different visceral metastatic patterns in prostate cancer patients.Methods We leveraged a prospective clinic-genomic cohort of 859 prostate cancer patients to identify 75 patients with visceral metastasis.Among them,there were 41 patients with lung metastasis and 34 patients with liver metastasis,respectively.All patients have available clinical and genomic data.We analyzed the association between visceral metastatic patterns and clinical-genomic characterization.Results The incidence of lung metastasis and liver metastasis in mCSPC were 9.3%and 3.0%,respectively,whereas the incidence in mCRPC were 6.2%and 9.1%,respectively.There was no significant association between metastatic patterns and clinical-genomic characterization.Notably,patients with liver metastasis were enriched with AR gain(38.2%vs 12.2%,P=0.013),CCND1 gain(20.6%vs 2.4%,P=0.02),PTEN loss(20.6%vs 2.4%,P=0.02),and BRCA2 loss(11.8%vs 0%,P=0.04).Conclusion More attention should be paid to lung metastasis for patients in mCSPC,while more attention should be paid to liver metastasis for patients in mCRPC.The difference in molecular basis indicated diverse treatment strategies should be adopted for patients with different visceral metastasis.