Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer
Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship betwe...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | World Journal of Surgical Oncology |
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| Online Access: | https://doi.org/10.1186/s12957-021-02137-1 |
| _version_ | 1819297712305078272 |
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| author | Lijun Xu Qing Zheng |
| author_facet | Lijun Xu Qing Zheng |
| author_sort | Lijun Xu |
| collection | DOAJ |
| description | Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels. |
| first_indexed | 2024-12-24T05:18:22Z |
| format | Article |
| id | doaj.art-fad6dd199c1248a2b8a42041a78f5338 |
| institution | Directory Open Access Journal |
| issn | 1477-7819 |
| language | English |
| last_indexed | 2024-12-24T05:18:22Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj.art-fad6dd199c1248a2b8a42041a78f53382022-12-21T17:13:31ZengBMCWorld Journal of Surgical Oncology1477-78192021-02-0119111210.1186/s12957-021-02137-1Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancerLijun Xu0Qing Zheng1Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Ministry of HealthDivision of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Ministry of HealthAbstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels.https://doi.org/10.1186/s12957-021-02137-1Colorectal cancerImmune checkpoint inhibitorsMicroRNAsTCGATumor mutational burden |
| spellingShingle | Lijun Xu Qing Zheng Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer World Journal of Surgical Oncology Colorectal cancer Immune checkpoint inhibitors MicroRNAs TCGA Tumor mutational burden |
| title | Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer |
| title_full | Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer |
| title_fullStr | Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer |
| title_full_unstemmed | Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer |
| title_short | Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer |
| title_sort | identification and validation of a mirna related expression signature for tumor mutational burden in colorectal cancer |
| topic | Colorectal cancer Immune checkpoint inhibitors MicroRNAs TCGA Tumor mutational burden |
| url | https://doi.org/10.1186/s12957-021-02137-1 |
| work_keys_str_mv | AT lijunxu identificationandvalidationofamirnarelatedexpressionsignaturefortumormutationalburdenincolorectalcancer AT qingzheng identificationandvalidationofamirnarelatedexpressionsignaturefortumormutationalburdenincolorectalcancer |