Abstract B43: Evaluation of a miRNA-mRNA panel for esophageal cancer detection
Authors: Sharma Priyanka , Saraya Anoop , Sharma Rinu 
Published: May 2016

Introduction: Esophageal Cancer (EC) is the sixth leading cause of deaths from cancer worldwide. Despite improvements in current therapeutic modalities, the diagnosis of EC patients is still dismal due to its asymptomatic nature and rapid progression. Identification of minimally invasive and reliable diagnostic markers may dramatically increase the survival of patients by improving the chances of timely detection and intervention. Recent studies have shown that a miRNA-mRNA based panel may serve as a fingerprint for detection of EC patients from normal subjects with increased sensitivity and specificity. Herein, we evaluated a miRNA-mRNA based signature including two miRNAs (miR-107 and miR-144) and their putative target mRNAs to be a potential diagnostic marker for EC.

Objectives: The objective of the present study was to analyze the diagnostic potential of a miRNA-mRNA based panel consisting of two miRNAs and their potential targets.

Materials and Methods: The expression of miR-107 and miR-144 were analyzed in EC tissues and their matched distant non-malignant tissues using quantitative real time PCR. The circulating levels of miR-107 and miR-144 were also analyzed in sera of esophageal cancer patients and normal subjects to determine their potential as noninvasive markers for esophageal cancer. Additionally, in order to evaluate the diagnostic potential of miRNA-mRNA based panel, the expression of potential targets of miR-107 and miR-144 were also determined in EC tissues as compared to their matched distant non-malignant tissues. Risk score analysis was performed to evaluate the association between miRNA/mRNA expression and EC. Linear regression models were then fitted to determine the contribution of each of the miRNA/mRNA to risk score function. ROC curves were then used to evaluate the diagnostic potential of the panel and to find out appropriate cut-off point. Pathway enrichment analysis was also carried out to find out the most significant pathways targeted by miR-107 and miR-144.

Results: The receiver operating characteristic curves indicated that the two miRNA panel (AUC=0.772, p=0.000) constitutes a more sensitive and specific diagnostic test compared with any single miRNA-based assay. Panel of circulating miRNAs also displayed a better performance compared with single miRNA assay in discriminating EC patients from normal controls. Most importantly, the miRNA-mRNA panel showed enhanced sensitivity (80%) and specificity (77.14%) in terms of discriminating EC tissues from adjacent non malignant tissues with an AUC of 0.835 as compared to two-miRNA panel. Pathway enrichment analysis for potential targets of miR-107 and miR-144 revealed four significant (p&lt;0.010) pathways targeted by both the miRNAs viz. pathways in cancer, mTOR pathway, chronic myeloid leukemia and neurotrophin pathway.

Conclusion: Present study implied that the miRNA-mRNA panel may discriminate esophageal cancer tissues from non-malignant tissues with enhanced sensitivity and specificity as compared to single miRNA or mRNA based assay.

Citation Format: Priyanka Sharma, Anoop Saraya, Rinu Sharma. Evaluation of a miRNA-mRNA panel for esophageal cancer detection. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B43.