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Establishment and experimental validation of an immune miRNA signature for assessing prognosis and immune landscape of patients with colorectal cancer |
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| Authors: | Zaoqu Liu Taoyuan Lu Yanli Wang Dechao Jiao Zhaonan Li Libo Wang Long Liu Chunguang Guo Yanan Zhao Xinwei Han |
| Affiliation: | 1. Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;2. Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Zhengzhou, China Contribution: Investigation (equal), Methodology (equal), Writing - original draft (equal);3. Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Contribution: Writing - original draft (equal), Writing - review & editing (equal);4. Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Contribution: Data curation (equal), Investigation (equal);5. Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Contribution: Writing - original draft (equal);6. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;7. Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Contribution: Writing - original draft (equal) |
| Abstract: | As essential regulators of gene expression, miRNAs are engaged in the initiation and progression of colorectal cancer (CRC), including antitumour immune response. In this study, we proposed an integrated algorithm, ImmuMiRNA, for identifying miRNA modulators of immune-associated pathways. Based on these immune-associated miRNAs, we applied the LASSO algorithm to develop a reliable and individualized signature for evaluating overall survival (OS) and inflammatory landscape of CRC patients. An external public data set and qRT-PCR data from 40 samples were further utilized to validate this signature. As a result, an immune-associated miRNA prognostic signature (IAMIPS) consisting of three miRNAs (miR-194-3P, miR-216a-5p and miR-3677-3p) was established and validated. Patients in the high-risk group possessed worse OS. After stratification for clinical factors, the signature remained a powerful independent predictor for OS. IAMIPS displayed much better accuracy than the traditional clinical stage in assessing the prognosis of CRC. Further analysis revealed that patients in the high-risk group were characterized by inflammatory response, abundance immune cell infiltration, and higher immune checkpoint profiles and tumour mutation burden (TMB). In conclusion, the IAMIPS is highly predictive of OS in patients with CRC, which may serve as a powerful prognostic tool to further optimize immunotherapies for cancer. |
| Keywords: | Colorectal cancer Immunotherapy MicroRNA Prognosis |