Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI, USA.
Adv Exp Med Biol. 2019;1210:111-120. doi: 10.1007/978-3-030-32656-2_6.
While the DNA of a tumor is often equated to a fingerprint or its unique genetic identify, a tumor's RNA profile represents a complex dynamic state more akin to a tumors personality or distinct behavior. Of the 11 types of RNA, the translational and clinical focus in prostate cancer has been primarily on mRNA and lncRNA. The most common use of RNA-based biomarkers is to assess a tumor's aggressiveness or treatment sensitivity. However, multiple gene expression signatures have been developed to capture the functional state that results from canonical DNA alterations, including ERG fusions, SPOP mutations, and Rb loss. More commonly, these biomarkers have been used to develop over 30 prognostic gene expression signatures, three of which are now commercially available and being increasingly incorporated into clinical trials. In parallel, the ability to use microarray and RNAseq technologies have allowed high throughput methods of performing whole transcriptomic analyses. This has enabled the discovery and training of numerous predictive biomarker signatures rooted in biologically informed pathways to determine which tumors are more sensitive or resistant to various treatments, including androgen-deprivation therapy, radiotherapy, chemotherapy, and PARP inhibition. This chapter will review the various types of RNA, technologies available to assess gene expression, and describe the available gene expression signatures for prostate cancer.
虽然肿瘤的 DNA 通常被等同于指纹或其独特的遗传标识，但肿瘤的 RNA 图谱代表了一种更类似于肿瘤个性或独特行为的复杂动态状态。在 11 种 RNA 中，前列腺癌的翻译和临床重点主要集中在 mRNA 和 lncRNA 上。基于 RNA 的生物标志物最常见的用途是评估肿瘤的侵袭性或治疗敏感性。然而，已经开发了多种基因表达特征来捕获源自规范 DNA 改变的功能状态，包括 ERG 融合、SPOP 突变和 Rb 缺失。更常见的是，这些生物标志物已被用于开发 30 多个预后基因表达特征，其中有 3 个现在可商业化，并越来越多地被纳入临床试验。与此同时，使用微阵列和 RNAseq 技术的能力允许进行高通量的全转录组分析。这使得能够发现和训练许多基于生物学信息途径的预测生物标志物特征，以确定哪些肿瘤对各种治疗方法（包括雄激素剥夺疗法、放疗、化疗和 PARP 抑制）更敏感或更耐药。本章将回顾各种类型的 RNA、评估基因表达的可用技术，并描述前列腺癌的现有基因表达特征。
