Prostate cancer (PCa), the most frequent and second most lethal cancer type in men in developed countries, is a highly heterogeneous disease. PCa heterogeneity, therapy resistance, stemness, and lethal progression have been attributed to lineage plasticity, which refers to the ability of neoplastic cells to undergo phenotypic changes under microenvironmental pressures by switching between developmental cell states. What remains to be elucidated is how to identify measurements of lineage plasticity, how to implement them to inform preclinical and clinical research, and, further, how to classify patients and inform therapeutic strategies in the clinic. Recent research has highlighted the crucial role of next-generation sequencing technologies in identifying potential biomarkers associated with lineage plasticity. Here, we review the genomic, transcriptomic, and epigenetic events that have been described in PCa and highlight those with significance for lineage plasticity. We further focus on their relevance in PCa research and their benefits in PCa patient classification. Finally, we explore ways in which bioinformatic analyses can be used to determine lineage plasticity based on large omics analyses and algorithms that can shed light on upstream and downstream events. Most importantly, an integrated multiomics approach may soon allow for the identification of a lineage plasticity signature, which would revolutionize the molecular classification of PCa patients.
前列腺癌（PCa）是发达国家男性中最常见且致死率第二高的癌症类型，是一种高度异质性的疾病。前列腺癌的异质性、治疗抵抗性、干细胞特性及致死性进展均与谱系可塑性密切相关。谱系可塑性指肿瘤细胞在微环境压力下通过转换发育细胞状态而发生表型变化的能力。目前亟待阐明的是：如何建立谱系可塑性的评估体系，如何将其应用于指导临床前及临床研究，以及如何基于此对患者进行分类并制定临床治疗策略。近期研究凸显了新一代测序技术在识别与谱系可塑性相关潜在生物标志物中的关键作用。本文系统综述了前列腺癌中已报道的基因组、转录组和表观遗传学事件，重点探讨了与谱系可塑性相关的重要发现。我们进一步聚焦这些发现在前列腺癌研究中的意义及其在患者分类中的应用价值。最后，我们探索了如何通过生物信息学分析，基于大规模组学数据和算法解析谱系可塑性的上下游事件。最重要的是，整合多组学分析方法有望在不久的将来建立谱系可塑性特征图谱，这将彻底革新前列腺癌患者的分子分型体系。
肿瘤(癌症)患者之家