RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer
Qin Li,
Ziteng Li,
Bing Chen,
Jingjing Zhao,
Hongwu Yu,
Jia Hu,
Hongyan Lai,
Hena Zhang,
Yan Li,
Zhiqiang Meng,
Zhixiang Hu,
Shenglin Huang
Affiliations
Qin Li
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, and Institute of Pathology, Fudan University, Shanghai 200032, China
Ziteng Li
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Bing Chen
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Jingjing Zhao
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Hongwu Yu
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Jia Hu
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Hongyan Lai
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Hena Zhang
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Yan Li
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Zhiqiang Meng
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding author
Zhixiang Hu
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding author
Shenglin Huang
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding author
Summary: RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable-element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate putative neoantigens for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.
