Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer
Abstract Background Colorectal cancer is considered as the second most common cancer worldwide. Studies have shown that m6A RNA methylation abnormalities play an important role in the pathogenesis of many human diseases, including cancer. The current study was designed to characterize the mutation o...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-023-01509-8 |
| _version_ | 1797822621205659648 |
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| author | Tao Jiang Linshuai Xing Lipeng Zhao Ziqi Ye Dong Yu Shengtao Lin |
| author_facet | Tao Jiang Linshuai Xing Lipeng Zhao Ziqi Ye Dong Yu Shengtao Lin |
| author_sort | Tao Jiang |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer is considered as the second most common cancer worldwide. Studies have shown that m6A RNA methylation abnormalities play an important role in the pathogenesis of many human diseases, including cancer. The current study was designed to characterize the mutation of m6A related genes and explore their prognostic role in colorectal cancer. Methods RNA-seq data and somatic mutation data of TCGA-COAD and TCGA-READ were downloaded from UCSC xena for comprehensive analysis. M6A related genes were selected from previous literatures, including "Writer" protein (METTL3, METTL5, METTL14, METTL16, ZC3H13, RBM15, WTAP, KIAA1429), "Reader" protein YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, HNRNPC, IGF2BP1, IGF2BP2, IGF2BP3), and "Eraser" protein (FTO, ALKBH5). Kaplan–Meier diagrams were used to explore the correlation between m6A-related genes and colorectal cancer prognosis. The correlations between m6A-related genes and clinical parameters and immune-related indicators were explored by Spearman correlation analysis. And finally, the expression patterns of five key genes (RBMX, FMR1, IGF2BP1, LRPPRC and YTHDC2) were detected by qPCR in CRC specimens. Results In CRC, the expressions of m6A-related genes were significantly different between CRC and normal control except METTL14, YTHDF2, YTHDF3. Some of CRC patients (178 in 536) have a m6A-related genes mutation. ZC3H13 has highest mutation frequency of all m6A-related genes. M6A-related genes mainly enrich in regulation of mRNA metabolic process pathway. Patients with high expressions of FMR1, LRPPRC, METTL14, RBMX, YTHDC2, YTHDF2, YTHDF3 have poor prognosis in CRC. There was a significant correlation between the FMR1, LRPPRC, RBMX, YTHDC2, IGF2BP1 expression and the clinical characteristics of CRC. In addition, these genes are significantly associated with immune-related indicators. According to the expression patterns of FMR1, LRPPRC, RBMX, YTHDC2, and IGF2BP1, patients with CRC were clustered into two groups, and their survival was significantly different. By evaluating the tumor microenvironment in two clusters using ssGSEA, expressions of immune checkpoints and GSVA enrichment analysis, we observed that the immune and stem cell index of two cluster were much different. The qPCR results showed that RBMX expression was markedly elevated in cancerous tissues than in the normal colonic tissues. Conclusion Our study identified novel prognostic markers associated with immune of CRC cancer patients. Moreover, the potential mechanisms of prognostic markers in regulating the etiology of CRC cancer were investigated. These findings enrich our understanding of the relationships between m6a related genes and CRC, and may provide novel ideas in the therapy of CRC patients. |
| first_indexed | 2024-03-13T10:11:49Z |
| format | Article |
| id | doaj.art-b211a55f3c6b4c318e5704e52dfb9e30 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-13T10:11:49Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj.art-b211a55f3c6b4c318e5704e52dfb9e302023-05-21T11:29:35ZengBMCBMC Medical Genomics1755-87942023-05-0116111510.1186/s12920-023-01509-8Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancerTao Jiang0Linshuai Xing1Lipeng Zhao2Ziqi Ye3Dong Yu4Shengtao Lin5Department of Anal-Colorectal Surgery, General Hospital of Ningxia Medical UniversitySchool of Clinical Medicine, Ningxia Medical UniversitySchool of Clinical Medicine, Ningxia Medical UniversitySchool of Clinical Medicine, Ningxia Medical UniversityDepartment of Anal-Colorectal Surgery, General Hospital of Ningxia Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityAbstract Background Colorectal cancer is considered as the second most common cancer worldwide. Studies have shown that m6A RNA methylation abnormalities play an important role in the pathogenesis of many human diseases, including cancer. The current study was designed to characterize the mutation of m6A related genes and explore their prognostic role in colorectal cancer. Methods RNA-seq data and somatic mutation data of TCGA-COAD and TCGA-READ were downloaded from UCSC xena for comprehensive analysis. M6A related genes were selected from previous literatures, including "Writer" protein (METTL3, METTL5, METTL14, METTL16, ZC3H13, RBM15, WTAP, KIAA1429), "Reader" protein YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, HNRNPC, IGF2BP1, IGF2BP2, IGF2BP3), and "Eraser" protein (FTO, ALKBH5). Kaplan–Meier diagrams were used to explore the correlation between m6A-related genes and colorectal cancer prognosis. The correlations between m6A-related genes and clinical parameters and immune-related indicators were explored by Spearman correlation analysis. And finally, the expression patterns of five key genes (RBMX, FMR1, IGF2BP1, LRPPRC and YTHDC2) were detected by qPCR in CRC specimens. Results In CRC, the expressions of m6A-related genes were significantly different between CRC and normal control except METTL14, YTHDF2, YTHDF3. Some of CRC patients (178 in 536) have a m6A-related genes mutation. ZC3H13 has highest mutation frequency of all m6A-related genes. M6A-related genes mainly enrich in regulation of mRNA metabolic process pathway. Patients with high expressions of FMR1, LRPPRC, METTL14, RBMX, YTHDC2, YTHDF2, YTHDF3 have poor prognosis in CRC. There was a significant correlation between the FMR1, LRPPRC, RBMX, YTHDC2, IGF2BP1 expression and the clinical characteristics of CRC. In addition, these genes are significantly associated with immune-related indicators. According to the expression patterns of FMR1, LRPPRC, RBMX, YTHDC2, and IGF2BP1, patients with CRC were clustered into two groups, and their survival was significantly different. By evaluating the tumor microenvironment in two clusters using ssGSEA, expressions of immune checkpoints and GSVA enrichment analysis, we observed that the immune and stem cell index of two cluster were much different. The qPCR results showed that RBMX expression was markedly elevated in cancerous tissues than in the normal colonic tissues. Conclusion Our study identified novel prognostic markers associated with immune of CRC cancer patients. Moreover, the potential mechanisms of prognostic markers in regulating the etiology of CRC cancer were investigated. These findings enrich our understanding of the relationships between m6a related genes and CRC, and may provide novel ideas in the therapy of CRC patients.https://doi.org/10.1186/s12920-023-01509-8Colorectal cancerImmunem6APrognosis |
| spellingShingle | Tao Jiang Linshuai Xing Lipeng Zhao Ziqi Ye Dong Yu Shengtao Lin Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer BMC Medical Genomics Colorectal cancer Immune m6A Prognosis |
| title | Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer |
| title_full | Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer |
| title_fullStr | Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer |
| title_full_unstemmed | Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer |
| title_short | Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer |
| title_sort | comprehensive analysis of m6a related gene mutation characteristics and prognosis in colorectal cancer |
| topic | Colorectal cancer Immune m6A Prognosis |
| url | https://doi.org/10.1186/s12920-023-01509-8 |
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