m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine
BackgroundThe RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049435/full |
| _version_ | 1811210683323252736 |
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| author | Baoxiang Chen Baoxiang Chen Baoxiang Chen Yiqing Xi Jianhong Zhao Jianhong Zhao Yuntian Hong Yuntian Hong Yuntian Hong Shunhua Tian Shunhua Tian Shunhua Tian Xiang Zhai Xiang Zhai Xiang Zhai Quanjiao Chen Xianghai Ren Xianghai Ren Xianghai Ren Lifang Fan Xiaoyu Xie Xiaoyu Xie Xiaoyu Xie Congqing Jiang Congqing Jiang Congqing Jiang |
| author_facet | Baoxiang Chen Baoxiang Chen Baoxiang Chen Yiqing Xi Jianhong Zhao Jianhong Zhao Yuntian Hong Yuntian Hong Yuntian Hong Shunhua Tian Shunhua Tian Shunhua Tian Xiang Zhai Xiang Zhai Xiang Zhai Quanjiao Chen Xianghai Ren Xianghai Ren Xianghai Ren Lifang Fan Xiaoyu Xie Xiaoyu Xie Xiaoyu Xie Congqing Jiang Congqing Jiang Congqing Jiang |
| author_sort | Baoxiang Chen |
| collection | DOAJ |
| description | BackgroundThe RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification.ResultsThe transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by “hot” TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy.ConclusionOur comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC. |
| first_indexed | 2024-04-12T04:59:00Z |
| format | Article |
| id | doaj.art-2c4466be49c0424fbceb0c70b079bbfd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T04:59:00Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2c4466be49c0424fbceb0c70b079bbfd2022-12-22T03:47:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10494351049435m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicineBaoxiang Chen0Baoxiang Chen1Baoxiang Chen2Yiqing Xi3Jianhong Zhao4Jianhong Zhao5Yuntian Hong6Yuntian Hong7Yuntian Hong8Shunhua Tian9Shunhua Tian10Shunhua Tian11Xiang Zhai12Xiang Zhai13Xiang Zhai14Quanjiao Chen15Xianghai Ren16Xianghai Ren17Xianghai Ren18Lifang Fan19Xiaoyu Xie20Xiaoyu Xie21Xiaoyu Xie22Congqing Jiang23Congqing Jiang24Congqing Jiang25Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaDepartment of Breast and Thyroid Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, ChinaFrontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, ChinaDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, CAS Center for Influenza Research and Early Warning, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaDepartment of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaClinical Center of Intestinal and Colorectal Diseases of Hubei Province (Zhongnan Hospital of Wuhan University), Wuhan, ChinaHubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan, ChinaBackgroundThe RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification.ResultsThe transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by “hot” TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy.ConclusionOur comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049435/full5-methylcytosineRNA methylationcolorectal cancerimmune infiltratestumor microenvironmentprecision medicine |
| spellingShingle | Baoxiang Chen Baoxiang Chen Baoxiang Chen Yiqing Xi Jianhong Zhao Jianhong Zhao Yuntian Hong Yuntian Hong Yuntian Hong Shunhua Tian Shunhua Tian Shunhua Tian Xiang Zhai Xiang Zhai Xiang Zhai Quanjiao Chen Xianghai Ren Xianghai Ren Xianghai Ren Lifang Fan Xiaoyu Xie Xiaoyu Xie Xiaoyu Xie Congqing Jiang Congqing Jiang Congqing Jiang m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine Frontiers in Immunology 5-methylcytosine RNA methylation colorectal cancer immune infiltrates tumor microenvironment precision medicine |
| title | m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine |
| title_full | m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine |
| title_fullStr | m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine |
| title_full_unstemmed | m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine |
| title_short | m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine |
| title_sort | m5c regulator mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer one step closer to precision medicine |
| topic | 5-methylcytosine RNA methylation colorectal cancer immune infiltrates tumor microenvironment precision medicine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049435/full |
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