A six-microRNA signature can better predict overall survival of patients with esophagus adenocarcinoma.

Tian Lan,Zunqiang Xiao,Zujian Hu,Yunyan Lu,Haibin Xu,Weimin Mao,Junling He

doi:10.7717/peerj.7353

Abstract

BackgroundThe microRNAs (miRNAs) have been validated as prognostic markers in many cancers. Here, we aimed at developing a miRNA-based signature for predicting the prognosis of esophagus adenocarcinoma (EAC).MethodsThe RNA-sequencing data set of EAC was downloaded from The Cancer Genome Atlas (TCGA). Eighty-four patients with EAC were classified into a training set and a test set randomly. Using univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), we identified prognostic factors and constructed a prognostic miRNA signature. The accuracy of the signature was evaluated by the receiver operating characteristic (ROC) curve.ResultIn general, in the training set, six miRNAs (hsa-mir-425, hsa-let-7b, hsa-mir-23a, hsa-mir-3074, hsa-mir-424 and hsa-mir-505) displayed good prognostic power as markers of overall survival for EAC patients. Relative to patients in the low-risk group, those assigned to the high-risk group according to their risk scores of the designed miRNA model displayed reduced overall survival. This 6-miRNA model was validated in test and entire set. The area under curve (AUC) for ROC at 3 years was 0.959, 0.840, and 0.868 in training, test, and entire set, respectively. Molecular functional analysis and pathway enrichment analysis indicated that the target messenger RNAs associated with 6-miRNA signature were closely related to several pathways involved in carcinogenesis, especially cell cycle.ConclusionIn summary, a novel 6-miRNA expression-based prognostic signature derived from the EAC data of TCGA was constructed and validated for predicting the prognosis of EAC.

Highlights

Esophagus cancer was ranked seventh among the leading types of cancers and sixth among the leading causes of cancer mortality in 2018 according to the Global Cancer Observatory (Fitzmaurice et al, 2018)
RNA-seq and clinicopathological data of esophagus adenocarcinoma (EAC) patients From The Cancer Genome Atlas (TCGA) data portal, RNA-seq data and associated clinical information were downloaded in January 2019
Based on the least absolute shrinkage and selection operator (LASSO) Cox regression models, a risk score was determined for each subject according to 6-miRNA status: Risk score 1⁄4 (-0.6089 Â hsa-let-7b) + (-0.1974 Â hsa-mir-23a) + (0.3369 Â hsa-mir-3074) + (0.0294 Â hsa-mir-424) + (0.2421 Â hsa-mir-425) + (0.2435 Â hsa-mir-505)

Summary

INTRODUCTION

Esophagus cancer was ranked seventh among the leading types of cancers and sixth among the leading causes of cancer mortality in 2018 according to the Global Cancer Observatory (Fitzmaurice et al, 2018). The predominant function of miRNAs is to regulate protein translation by binding to target messenger RNAs (mRNAs), and inhibit mRNA translation (Krol, Loedige & Filipowicz, 2010) They have recently been validated and applied in diagnosis and prognosis of a variety of tumors, including hepatocellular carcinoma (Parizadeh et al, 2019), prostate cancer (Moya et al, 2019), and breast cancer (Yerukala Sathipati & Ho, 2018). A 3-miRNA (miR-99b and miR-199a_3p and _5p) signature was correlated with patient survival and occurrence of lymph node metastasis (Feber et al, 2011). These findings were based on a small number of patients. Pathway enrichment and gene oncology annotation analyses were performed to understand the probable cellular functions of mRNAs associated with this signature

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