A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer

Zhenpeng Yang,1,2,* Shuai Lu,1,2,* Yuying Wang,1,2 Huazhen Tang,1,2 Bing Wang,1,2 Xibo Sun,1,3 Jinxiu Qu,1,2 Benqiang Rao1,2 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China; 3Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Benqiang Rao Tel +86 13521237767Email raobenqiang@bjsjth.cnObjective: This study aims at exploring the relationship between necroptosis-related miRNAs and colon cancer prognosis.Methods: We downloaded the miRNA sequencing data from the TCGA, and eight differentially expressed necroptosis-related miRNAs were screened. Then, we used Cox regression analysis to establish a prediction model of necroptosis-related miRNA. Finally, the prognosis related miRNAs were used to predict the target genes, and functional analysis was used to explore the potential mechanism of these target genes.Results: The miRNA-seq data of 444 COAD cases were downloaded from TCGA. We identified 8 differentially expressed miRNAs (has-miR-16-5p, has-miR-141-3p, has-miR-148a-3p, has-miR-425-5p, has-miR-7-5p, has-miR-223-3p, has-miR-200a-5p, and has-miR-500a-3p), then Cox analysis was performed for determining eight-miRNA signature prognostic biomarkers with obviously different OS. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for predicting 1-, 3-, and 5-year survival were 0.663, 0.653 and 0.639, respectively. The multivariate analysis also implied that the risk score was an independent prognostic factor considering other confounding factors (HR = 1.847, 95% CI = 1.197– 2.848, P = 0.006). According to the Kaplan–Meier analysis, the expression of hsa-miR-500a-3p (P = 0.003), hsa-miR-16-5p (P = 0.004) and hsa-miR-148a-3p (P = 0.035) significantly affected OS outcomes. We predicted the target genes of these three miRNAs and then screened 10 hub genes (CCND1, SMAD3, SMAD2, CDK1, TGFB2, CDC25A, CHEK1, VEGFA, CCNE1, WEE1). In addition, CHEK1 was associated with the survival prognosis.Conclusion: Our study demonstrated that necroptosis is closely associated with colon cancer, and the model of eight necroptosis-related miRNAs are potentially useful prognostic biomarkers and therapeutic targets for colon cancer.Keywords: necroptosis, colon cancer, prognosis