Amalric Amandine, Bastide Amandine, Attina Aurore, Choquet Armelle, Vialaret Jerome, Lehmann Sylvain, David Alexandre, Hirtz Christophe
IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.
University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France.
Crit Rev Clin Lab Sci. 2022 Jan;59(1):1-18. doi: 10.1080/10408363.2021.1958743. Epub 2021 Sep 2.
Despite significant progress in targeted therapies, cancer recurrence remains a major cause of mortality worldwide. Identification of accurate biomarkers, through molecular profiling in healthy and cancer patient samples, will improve diagnosis and promote personalized medicine. While genetic and epigenetic alterations of DNA are currently exploited as cancer biomarkers, their robustness is limited by tumor heterogeneity. Recently, cancer-associated changes in RNA marks have emerged as a promising source of diagnostic and prognostic biomarkers. RNA epigenetics (also known as epitranscriptomics) is an emerging field in which at least 150 chemical modifications in all types of RNA (mRNA, tRNA, lncRNA, rRNA, and microRNA) have been detected. These modifications fine-tune gene expression in both physiological and pathological processes. A growing number of studies have established links between specific modified nucleoside levels in solid/liquid biopsies, and cancer onset and progression. In this review, we highlight the potential role of epitranscriptomic markers in refining cancer diagnosis and/or prognosis. RNA modification patterns may contain important information for establishing an initial diagnosis, monitoring disease evolution, and predicting response to treatment. Furthermore, recent developments in mass spectrometry allow reliable quantification of RNA marks in solid biopsies and biological fluids. We discuss the great potential of mass spectrometry for identifying epitranscriptomic biomarker signatures in cancer diagnosis. While there are various methods to quantify modified nucleosides, most are unable to detect and quantify more than one type of RNA modification at a time. Mass spectrometry analyses, especially GC-MS/MS and LC-MS/MS, overcome this limitation and simultaneously detect modified nucleosides by multiple reaction monitoring. Indeed, several groups are currently validating mass spectrometry methods that quantify several nucleosides at one time in liquid biopsies. The challenge now is to exploit these powerful analytical tools to establish epitranscriptomic signatures that should open new perspectives in personalized medicine. This review summarizes the growing clinical field of analysis of RNA modifications and discusses pre-analytical and analytical approaches, focusing in particular on the development of new mass spectrometry tools and their clinical applications.
尽管靶向治疗取得了重大进展，但癌症复发仍然是全球范围内主要的死亡原因。通过对健康和癌症患者样本进行分子分析来鉴定准确的生物标志物，将改善诊断并推动个性化医疗。虽然DNA的遗传和表观遗传改变目前被用作癌症生物标志物，但其稳健性受到肿瘤异质性的限制。最近，RNA标记物中与癌症相关的变化已成为诊断和预后生物标志物的一个有前景的来源。RNA表观遗传学（也称为表观转录组学）是一个新兴领域，在所有类型的RNA（mRNA、tRNA、lncRNA、rRNA和microRNA）中已检测到至少150种化学修饰。这些修饰在生理和病理过程中对基因表达进行微调。越来越多的研究已经建立了实体/液体活检中特定修饰核苷水平与癌症发生和进展之间的联系。在本综述中，我们强调了表观转录组学标志物在优化癌症诊断和/或预后方面的潜在作用。RNA修饰模式可能包含用于建立初始诊断、监测疾病进展以及预测治疗反应的重要信息。此外，质谱技术的最新进展使得能够可靠地定量实体活检和生物体液中的RNA标记物。我们讨论了质谱技术在识别癌症诊断中表观转录组学生物标志物特征方面的巨大潜力。虽然有多种方法可以定量修饰核苷，但大多数方法一次只能检测和定量一种以上类型的RNA修饰。质谱分析，尤其是气相色谱-串联质谱（GC-MS/MS）和液相色谱-串联质谱（LC-MS/MS），克服了这一局限性，并通过多反应监测同时检测修饰核苷。事实上，目前有几个研究小组正在验证能够在液体活检中同时定量多种核苷的质谱方法。现在的挑战是利用这些强大的分析工具来建立表观转录组学特征，这应该会为个性化医疗开辟新的前景。本综述总结了RNA修饰分析这一不断发展的临床领域，并讨论了分析前和分析方法，特别关注新质谱工具的开发及其临床应用。
