Study of miRNA in Esophageal Cancer Potential Blood Based Biomarkers for Diagnosis

Abstract

Esophageal cancer (EC) is the eighth most common cancer and the sixth most common cause of death 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. Moreover. most of the current diagnostic methods are either invasive or lack sensitivity or specificity to diagnose esophageal cancer at early stages. The insidious symptomatology. rapid progression and lack of clinical predictive biomarkers for this disease lead to poor prognosis and limited success of therapeutic modalities. Therefore. identification of minimally invasive and reliable diagnostic markers may dramatically increase the survival of patients by improving the chances of timely detection and intervention. MicroRNA (miRNA) panel may serve as a fingerprint for EC detection with increased sensitivity and specificity. Herein, we analyzed the diagnostic potential of a six miRNA panel consisting of miR-21, miR-144, miR-107, miR-342, miR-93 and miR-152. The expression of miRNAs was analyzed in EC tissues and sera samples using qRT-PCR. Risk sc it analysis was performed and linear regression models were then fitted to generate the six miRNA panel. The ROC curve analysis indicated that the six miRNA panel (AUC=0.856) constitutes a more sensitive and specific diagnostic test in comparison to individual miRNAs. Most importantly, the panel of circulating miRNAs showed enhanced sensitivity (87.5%) and specificity (90.48%) in terms of discriminating EC patients from normal subjects with an AUC of 0.968. miR-107 and miR-144 were found to be significantly altered in EC tissues however indepth validation was warranted to elucidate their role in EC. Therefore, we further sought to determine their function in EC by either knockdown or overexpression of these miRNAs followed by invitro assays viz. MTT assay, cell cycle analysis by flow cytometry, annexin assay, colony formation assay, scratch assay and matrigel invasion assay. Overexpression of...