当前位置: X-MOL 学术Semin. Cancer Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Transcriptomics and solid tumors: The next frontier in precision cancer medicine
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2020-09-17 , DOI: 10.1016/j.semcancer.2020.09.007
Apostolia M Tsimberidou 1 , Elena Fountzilas 2 , Leonidas Bleris 3 , Razelle Kurzrock 4
Affiliation  

Transcriptomics, which encompasses assessments of alternative splicing and alternative polyadenylation, identification 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.



中文翻译:

转录组学和实体瘤:精准癌症医学的下一个前沿

转录组学包括对选择性剪接和选择性多聚腺苷酸化的评估、融合转录本的鉴定、非编码 RNA 的探索、转录本注释和新转录本的发现,是了解癌症机制和识别生物标志物的宝贵工具。高通量技术的最新进展使大规模基因表达谱成为可能。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个针对多种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,以将治疗与特定的分子改变相匹配。与单独的基因组分析相比,在 WINTHER 和其他试验中使用转录组分析增加了可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分析改善风险分层,鉴定驱动肿瘤的融合转录本,以及更好地理解影响随着一些基因组改变在 RNA 水平上被沉默,DNA 发生了变化。最后,RNA 测序和基因表达分析已被纳入临床试验,以识别预测免疫治疗反应的标志物。关于分析的复杂性、可重复性和可变性的许多问题,结果的解释仍然需要解决。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,从而加速精准肿瘤学的实施。

更新日期:2020-09-17
down
wechat
bug