A comprehensive expression landscape of RNA-binding proteins (RBPs) across 16 human cancer types

RNA-binding proteins (RBPs) are key regulators of posttranscriptional processes such as RNA maturation, localization, turnover and translation. Despite their dysregulation in various diseases including cancer, the landscape of RBP expression in human cancer has not been well elucidated. Here, we built a comprehensive expression landscape of 1504 RBPs across 16 human cancer types, which revealed that RBPs are predominantly upregulated in tumours and this phenomenon is affected by the tumour immune subtypes and microenvironment. Across different cancer types, 109 RBPs are consistently upregulated while 41 RBPs are consistently downregulated. These up-regulated and down-regulated RBPs show distinct molecular characteristics and prognostic effects, whereas their dysregulation is mediated by distinct cis/trans-regulatory mechanisms. Finally, we validated one candidate PABPC1L that might promote colon tumorigenesis by regulating mRNA splicing. In summary, we built a comprehensive expression landscape of RBPs across different cancer types and identified consistently dysregulated RBPs which could be novel targets for developing broad-spectrum anticancer agents.RNA结合蛋白（RNA-binding proteins, RBPs）是RNA成熟、定位、降解与翻译等转录后过程的关键调控因子。尽管RBPs在包括癌症在内的多种疾病中存在表达失调，但人类癌症中RBPs的表达全景尚未得到充分阐明。本研究针对16种人类癌症类型的1504个RBPs构建了全面的表达全景图谱，结果显示RBPs在肿瘤中普遍呈上调状态，且该现象受肿瘤免疫亚型与肿瘤微环境影响。在不同癌症类型中，共有109个RBPs呈现持续上调，41个RBPs呈现持续下调。这些上调与下调的RBPs具有独特的分子特征与预后效应，且其表达失调由不同的顺式/反式调控机制介导。最后，本研究验证了一个候选基因PABPC1L，其可能通过调控mRNA剪接促进结肠肿瘤发生。综上，本研究构建了覆盖不同癌症类型的RBPs全面表达全景图谱，并鉴定出持续失调的RBPs，这些分子可作为开发广谱抗癌药物的新型靶点。