Low Expression of MicroRNA335-5p Is Associated with Malignant Behavior of Gallbladder Cancer: A Clinicopathological Study

Abstract

Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cellular processes during cancer<br />progression, identified to be involved in tumorgenesis of several cancers including cancers of digestive system. However<br />its role in gallbladder inflammatory disease (GID) and gallbladder cancer (GBC) has not been well documented.<br />The present study was aimed to investigate the clinical significance of hsa-miRNA-335-5p (miR-335) in GBC and<br />GID. Subjects and Methods: This prospective case control study, conducted from July 1, 2014 to December 1, 2017<br />in Era's Lucknow Medical College & Hospital, India, evaluated miR-335 expression by real-time polymerase chain<br />reaction. Hundred tissue samples GID (control; n=50) and GBC (case; n=50) were studied. Relative quantification of<br />target miR-335 expression was examined using the comparative cycle threshold method. Their expression was correlated<br />with different clinicopathological parameters. Fishers' exact test, Student's t-test, and Chi-square test were used as<br />appropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rate.<br />Two sided PGBC lesions when compared with GID lesions (P<0.001). The low expression level of miR-335 was correlated with<br />histological grade (P=0.007), clinical stage (P<0.001), lymph node metastasis (P<0.001) and liver metastasis (P=0.016).<br />Reduced expression of miRNA-335 was associated with a shorter median overall survival (7 months vs. 25 months)<br />in GBC patients (P<0.001). Conclusions: Down regulation of miR-335 is associated with the severity of the disease<br />and thus indicate that miR-335 expression may serve as prognostic marker for GBC.