Despite significant advances in the diagnosis and treatment of cardiovascular diseases, recent calls have emphasized the unmet need to improve precision-based approaches in cardiovascular disease. Although some studies provide preliminary evidence of the diagnostic and prognostic potential of circulating coding and non-coding RNAs, the complex RNA biology and lack of standardization have hampered the translation of these markers into clinical practice. In this position paper of the CardioRNA COST action CA17129, we provide recommendations to standardize the RNA development process in order to catalyse efforts to investigate novel RNAs for clinical use. We list the unmet clinical needs in cardiovascular disease, such as the identification of high-risk patients with ischaemic heart disease or heart failure who require more intensive therapies. The advantages and pitfalls of the different sample types, including RNAs from plasma, extracellular vesicles, and whole blood, are discussed in the sample matrix, together with their respective analytical methods. The effect of patient demographics and highly prevalent comorbidities, such as metabolic disorders, on the expression of the candidate RNA is presented and should be reported in biomarker studies. We discuss the statistical and regulatory aspects to translate a candidate RNA from a research use only assay to an in-vitro diagnostic test for clinical use. Optimal planning of this development track is required, with input from the researcher, statistician, industry, and regulatory partners.

中文翻译：

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心血管疾病的外周血 RNA 生物标志物从实验室到临床：来自 EU-CardioRNA COST 行动 CA17129 的立场文件


尽管心血管疾病的诊断和治疗取得了重大进展，但最近的呼吁强调了改善心血管疾病精确治疗方法的需求尚未得到满足。尽管一些研究提供了循环编码和非编码 RNA 的诊断和预后潜力的初步证据，但复杂的 RNA 生物学和缺乏标准化阻碍了这些标记物转化为临床实践。在 CardioRNA COST 行动 CA17129 的立场文件中，我们提供了标准化 RNA 开发过程的建议，以促进研究临床用途的新型 RNA 的努力。我们列出了心血管疾病方面未满足的临床需求，例如识别需要更强化治疗的缺血性心脏病或心力衰竭高危患者。样品基质中讨论了不同样品类型（包括来自血浆、细胞外囊泡和全血的 RNA）的优点和缺点，以及它们各自的分析方法。患者人口统计数据和高度普遍的合并症（例如代谢紊乱）对候选 RNA 表达的影响已在生物标志物研究中提出并应报告。我们讨论了统计和监管方面的问题，以将候选 RNA 从仅供研究使用的测定转化为临床使用的体外诊断测试。需要根据研究人员、统计学家、行业和监管合作伙伴的意见，对这一发展轨迹进行优化规划。