Transcriptomics and solid tumors: The next frontier in precision cancer medicine
Transcriptomics and solid tumors: The next frontier in precision cancer medicine
复制标题
转录组学和实体肿瘤：精准癌症医学的下一个前沿
DOI：
10.1016/j.semcancer.2020.09.007
复制
发表时间：
2022-09-01
影响因子：
14.5
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
--
作者：
Tsimberidou, Apostolia M.;Fountzilas, Elena;Kurzrock, Razelle
转录组学包括可变剪接和可变多聚腺苷酸化的评估、融合转录物的鉴定、非编码RNA的探索、转录物注释和新转录物的发现，是理解癌症机制和鉴定生物标志物的有价值的工具。高通量技术的最新进展使大规模基因表达谱分析成为可能。重要的是，肿瘤组织的RNA表达谱已成功用于确定临床上可操作的分子改变。WINTHER精准医学临床试验是第一项针对不同实体恶性肿瘤的前瞻性试验，该试验评估了基因组学和转录组学，以将治疗与特定分子改变相匹配。在WINTHER和其他试验中使用转录组分析与单独的基因组分析相比增加了靶向组学变化的数量。转录组学的其他应用包括评估肿瘤和循环非编码RNA作为预测和预后生物标志物，通过使用预后和预测性多基因测定来改善风险分层，鉴定驱动肿瘤的融合转录物，以及更好地理解DNA变化的影响，因为一些基因组改变在RNA水平上沉默。最后，RNA测序和基因表达分析已被纳入临床试验，以确定预测免疫治疗反应的标志物。关于分析的复杂性，其可重复性和可变性以及结果的解释的许多问题仍然需要解决。转录组学与基因组学、蛋白质组学、表观遗传学和肿瘤免疫分析的整合将改善生物标志物的发现和我们对疾病机制的理解，从而加速精确肿瘤学的实施。
Transcriptomics, which encompasses assessments of alternative splicing and alternative polyadenylation, iden-tification of fusion transcripts, explorations of noncoding RNAs, transcript annotation, and discovery of novel transcripts, is a valuable tool for understanding cancer mechanisms and identifying biomarkers. Recent advances in high-throughput technologies have enabled large-scale gene expression profiling. Importantly, RNA expression profiling of tumor tissue has been successfully used to determine clinically actionable molecular alterations. The WINTHER precision medicine clinical trial was the first prospective trial in diverse solid malignancies that assessed both genomics and transcriptomics to match treatments to specific molecular alterations. The use of transcriptome analysis in WINTHER and other trials increased the number of targetable-omic changes compared to genomic profiling alone. Other applications of transcriptomics involve the evaluation of tumor and circulating noncoding RNAs as predictive and prognostic biomarkers, the improvement of risk stratification by the use of prognostic and predictive multigene assays, the identification of fusion transcripts that drive tumors, and an improved understanding of the impact of DNA changes as some genomic alterations are silenced at the RNA level. Finally, RNA sequencing and gene expression analysis have been incorporated into clinical trials to identify markers predicting response to immunotherapy. Many issues regarding the complexity of the analysis, its reproducibility and variability, and the interpretation of the results still need to be addressed. The integration of transcriptomics with genomics, proteomics, epigenetics, and tumor immune profiling will improve biomarker discovery and our understanding of disease mechanisms and, thereby, accelerate the implementation of precision oncology.