Identification of a 4‐miRNA signature as a potential prognostic biomarker for pancreatic adenocarcinoma

Abstract

An microRNA (miRNA) signature to predict the clinical outcome of pancreatic adenocarcinoma (PAAD) is still lacking. In the current study, we aimed at identifying and evaluating a prognostic miRNA signature for patients with PAAD. The miRNA expression profile and the clinical information regarding patients with PAAD were recruited from The Cancer Genome Atlas database. Differentially expressed miRNAs were identified between normal and tumor samples. By means of survival analysis, a 4‐miRNA signature for predicting patients' with PAAD overall survival (OS) was constructed. Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of survival prediction. Furthermore, the biological function of the predicted miRNAs was evaluated using a bioinformatics approach. Four (hsa‐mir‐126, hsa‐mir‐3613, hsa‐mir‐424, and hsa‐mir‐4772) out of 17 differentially expressed miRNAs were associated to the OS of patients with PAAD. Moreover, the area under the curve (AUC) of the constructed 4‐miRNA signature associated to patients' with PAAD 2‐year survival was 0.789. The multivariate Cox's proportional hazards regression model suggested that this 4‐miRNA signature was an independent prognostic factor of other clinical parameters in patients with PAAD. Further pathway enrichment analyses revealed that the miRNAs in the 4‐miRNA signature might regulate genes that affect focal adhesion, Wnt signaling pathway, and PI3K‐Akt signaling pathway. Thus, these findings indicated that the 4‐miRNA signature might be an effective independent prognostic biomarker in the prediction of PAAD patients' survival.

MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F7

“…proved to be a potential prognostic biomarker for some cancers in some studies [21,22]. Besides, miR-424 can suppress the metastasis and invasion of HCC [23].…”

m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer

“…Moreover, GLI1 co-expressed and DEGs between tumor samples and normal tissues were both largely enriched in the PI3K-Akt pathway in STAD (Yu et al, 2018;Li et al, 2019). In PAAD, 4-miRNA as independent prognostic factor was found to be related to the PI3K-Akt signaling pathway (Wang et al, 2019). Growing evidence revealed that the ErbB and PI3K-Akt signaling pathways play vital roles in colorectal cancer by regulating microRNA, lncRNA, mRNA, etc.…”

Prediction of pancreatic adenocarcinoma patient risk status using alternative splicing events

“…We have analyzed the performance of our final prognostic model in comparison with the previously identified prognostic markers obtained from several published studies. We observed that our splice event based seven gene prognostic model (HR = 9.13; P-value = 6.42e-10, Concordance = 0.7; and 5yr AUC = 0.93) outperformed the existing PAAD specific prognostic markers such as five miRNAs (HR = 0.13; P < 0.001) (Liang et al, 2018) and four miRNAs based prognostic models (HR= 2.8; P < 0.001; 2yr AUC = 0.79) (Wang, Deng, & Ma, 2019), 20 gene-based prognostic signature (HR = 2.01; P = 0.007) (Canlı et al, 2020), three lncRNA signature (P < 0.001; AUC = 0.72) (Shi et al, 2018), 29 gene-based ceRNA signature (HR = 1.66; P < 1.0e-04) (Zhao & Liu, 2017); 9 gene prognostic signature (P < 0.0001; 1yr AUC = 0.70) (Wu, Li, Zhang, Liu, & Zhao, 2019), and 7 gene-based AS event prognostic signature (AUC = 0.89) (Yu et al, 2019). Our splice-event based prognostic marker also outperformed an exisiting study in terms of HR and AUC that evaluates the risk assessment capability of PAAD related AS events (Xu, Pan, Ding, & Pan, 2020).…”