The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer
Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explor...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-10-01
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| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.1177/11795549231203150 |
| _version_ | 1797648822345662464 |
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| author | Lamei Zhao Dongyan Han Jianghua Zhu Dexi Bi Tingting Ding Xingchen Zhu Dengfeng Huang Youhua Zhang Ling Lu Weijun Wu Yaohui Gao Hu Liu Qiongyi Huang Qing Wei Xudong Yao |
| author_facet | Lamei Zhao Dongyan Han Jianghua Zhu Dexi Bi Tingting Ding Xingchen Zhu Dengfeng Huang Youhua Zhang Ling Lu Weijun Wu Yaohui Gao Hu Liu Qiongyi Huang Qing Wei Xudong Yao |
| author_sort | Lamei Zhao |
| collection | DOAJ |
| description | Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation. |
| first_indexed | 2024-03-11T15:37:30Z |
| format | Article |
| id | doaj.art-b5e36c3b313347eb9b33786058032943 |
| institution | Directory Open Access Journal |
| issn | 1179-5549 |
| language | English |
| last_indexed | 2024-03-11T15:37:30Z |
| publishDate | 2023-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj.art-b5e36c3b313347eb9b337860580329432023-10-26T14:33:44ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492023-10-011710.1177/11795549231203150The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder CancerLamei Zhao0Dongyan Han1Jianghua Zhu2Dexi Bi3Tingting Ding4Xingchen Zhu5Dengfeng Huang6Youhua Zhang7Ling Lu8Weijun Wu9Yaohui Gao10Hu Liu11Qiongyi Huang12Qing Wei13Xudong Yao14Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaMedical Equipment of Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaBackground: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.https://doi.org/10.1177/11795549231203150 |
| spellingShingle | Lamei Zhao Dongyan Han Jianghua Zhu Dexi Bi Tingting Ding Xingchen Zhu Dengfeng Huang Youhua Zhang Ling Lu Weijun Wu Yaohui Gao Hu Liu Qiongyi Huang Qing Wei Xudong Yao The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer Clinical Medicine Insights: Oncology |
| title | The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer |
| title_full | The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer |
| title_fullStr | The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer |
| title_full_unstemmed | The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer |
| title_short | The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer |
| title_sort | rna m6a binding protein ythdc1 is downregulated and associated with m2 macrophage infiltration in muscle invasive bladder cancer |
| url | https://doi.org/10.1177/11795549231203150 |
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