Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis
Alternative splicing can produce transcripts that affect cancer development and thus shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been studied less in cancer biology research. Here, we generated a pan-cancer IR landscape for...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/23/5689 |
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| author | Leihuan Huang Xin Zeng Haijing Ma Yu Yang Yoshie Akimoto Gang Wei Ting Ni |
| author_facet | Leihuan Huang Xin Zeng Haijing Ma Yu Yang Yoshie Akimoto Gang Wei Ting Ni |
| author_sort | Leihuan Huang |
| collection | DOAJ |
| description | Alternative splicing can produce transcripts that affect cancer development and thus shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been studied less in cancer biology research. Here, we generated a pan-cancer IR landscape for more than 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). We characterized differentially retained introns between tumor and normal samples and identified retained introns associated with survival. We discovered 988 differentially retained introns in 14 cancers, some of which demonstrated diagnostic potential in multiple cancer types. We also inferred a large number of prognosis-related introns in 33 cancer types, and the associated genes included well-known cancer hallmarks such as angiogenesis, metastasis, and DNA mutations. Notably, we discovered a novel intron retention inside the 5′UTR of <i>STN1</i> that is associated with the survival of lung cancer patients. The retained intron reduces translation efficiency by producing upstream open reading frames (uORFs) and thereby inhibits colony formation and cell migration of lung cancer cells. Besides, the IR-based prognostic model achieved good stratification in certain cancers, as illustrated in acute myeloid leukemia. Taken together, we performed a comprehensive IR survey at a pan-cancer level, and the results implied that IR has the potential to be diagnostic and prognostic cancer biomarkers, as well as new drug targets. |
| first_indexed | 2024-03-09T01:53:27Z |
| format | Article |
| id | doaj.art-078dabdf8e784f9db915d2e5d8f5655a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T01:53:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-078dabdf8e784f9db915d2e5d8f5655a2023-12-08T15:12:57ZengMDPI AGCancers2072-66942023-12-011523568910.3390/cancers15235689Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and PrognosisLeihuan Huang0Xin Zeng1Haijing Ma2Yu Yang3Yoshie Akimoto4Gang Wei5Ting Ni6State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, ChinaIskra Industry Co., Ltd., Tokyo 103-0027, JapanState Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, ChinaAlternative splicing can produce transcripts that affect cancer development and thus shows potential for cancer diagnosis and treatment. However, intron retention (IR), a type of alternative splicing, has been studied less in cancer biology research. Here, we generated a pan-cancer IR landscape for more than 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). We characterized differentially retained introns between tumor and normal samples and identified retained introns associated with survival. We discovered 988 differentially retained introns in 14 cancers, some of which demonstrated diagnostic potential in multiple cancer types. We also inferred a large number of prognosis-related introns in 33 cancer types, and the associated genes included well-known cancer hallmarks such as angiogenesis, metastasis, and DNA mutations. Notably, we discovered a novel intron retention inside the 5′UTR of <i>STN1</i> that is associated with the survival of lung cancer patients. The retained intron reduces translation efficiency by producing upstream open reading frames (uORFs) and thereby inhibits colony formation and cell migration of lung cancer cells. Besides, the IR-based prognostic model achieved good stratification in certain cancers, as illustrated in acute myeloid leukemia. Taken together, we performed a comprehensive IR survey at a pan-cancer level, and the results implied that IR has the potential to be diagnostic and prognostic cancer biomarkers, as well as new drug targets.https://www.mdpi.com/2072-6694/15/23/5689intron retentionRNA-seqcancerdiagnosisprognosis |
| spellingShingle | Leihuan Huang Xin Zeng Haijing Ma Yu Yang Yoshie Akimoto Gang Wei Ting Ni Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis Cancers intron retention RNA-seq cancer diagnosis prognosis |
| title | Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis |
| title_full | Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis |
| title_fullStr | Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis |
| title_full_unstemmed | Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis |
| title_short | Pan-Cancer Profiling of Intron Retention and Its Clinical Significance in Diagnosis and Prognosis |
| title_sort | pan cancer profiling of intron retention and its clinical significance in diagnosis and prognosis |
| topic | intron retention RNA-seq cancer diagnosis prognosis |
| url | https://www.mdpi.com/2072-6694/15/23/5689 |
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