Development of a Novel Six-miRNA-Based Model to Predict Overall Survival Among Colon Adenocarcinoma Patients

Introduction: Colon carcinoma is a common malignant tumor worldwide. Accurately predicting prognosis of colon adenocarcinoma (CA) patients may facilitate clinical individual decision-making. Many studies have reported that microRNAs (miRNAs) were associated with prognosis for patients with colon carcinoma. This study aimed to identify the prognosis-related miRNAs for predicting the overall survival (OS) of CA patients. Methods: Firstly, we analyzed the CA datasets from the Cancer Genome Atlas (TCGA), and looked for the prognosis-related miRNAs. Then, we developed a novel prediction model based on these miRNAs and the clinical characteristics. Time-dependent receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the discrimination and accuracy of the signature and model. Finally, cell function assays and bioinformatics analyses were performed to evaluate the role of these selected miRNAs in modulating biological process in CA. Results: Six prognosis-related miRNAs were included in the miRNA-based signature, and it could effectively distinguish low-risk patients and high-risk patients. Furthermore, we established a prognostic model incorporating the six-miRNA-based signature and clinical characteristics. Areas under curves (AUCs) indicated that the six-miRNA-based model has a better predictive ability than TNM stage (AUC: 0.805 vs. 0.694). The calibration plots suggested close agreement between model predictions and actual observations. GO analysis showed that the target genes of these miRNAs are mainly involved in enrichment in protein binding and regulation of transcript and cytosol. KEGG pathway enrichment analysis indicated that these genes were mainly enriched in PI3K-Akt signaling pathway. Finally, we found that the five miRNAs except miR-152 were upregulated in tumor tissues and CA cells. The functional experiments revealed that miR-1245a, miR-3682, miR-33b, and miR-5683 promoted the migratory abilities and proliferation of CA cell, whereas miR-152 showed opposite effects. However, miR-4444-2 did not influence the migratory ability and proliferation of CA cell. Conclusions: In conclusion, we developed a novel six-miRNA-based model to predict 5-year survival probabilities for CA patients. This model has the potential to facilitate individualized treatment decisions.