Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan–Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.
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Research code that was used to implement methods described in this study is publicly available on GitHub: https://github.com/yjzhang2013/OncoSplicing.
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The authors would like to thank Xudong Zhang of Genek Company for helpful advices of data processing. This work was funded by the National Natural Science Foundation of China (81702522, 81602236) and National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304022).
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The authors declare that they have no conflict of interest.
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Zhang, Y., Yan, L., Zeng, J. et al. Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers. Oncogene 38, 6678–6695 (2019). https://doi.org/10.1038/s41388-019-0910-7
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