Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer

小RNA 医学 结直肠癌 肿瘤科 队列 癌症 内科学 计算生物学 生物信息学 癌症研究 生物 遗传学 基因
作者
Lijun Xu,Qing Zheng
出处
期刊:World Journal of Surgical Oncology [Springer Nature]
卷期号:19 (1) 被引量:10
标识
DOI:10.1186/s12957-021-02137-1
摘要

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 TMB high group and the TMB low 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 (AUC test 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.
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