Evaluation of Roles of MicroRNA-21 and MicroRNA-18a in Esophageal Squamous Cell Carcinoma and Comparison of Their Changes in Expression Post-Chemoradiotherapy

BACKGROUND: A number of circulating microRNAs (miRNAs) have been reported to be highly expressed in several cancers; whether their expression is associated with clinicopathological factors and prognosis in patients of esophageal squamous cell carcinoma (ESCC) is still under investigation. Although studies have demonstrated their overexpression in tissues of ESCC, there are limited data for circulating miRNAs. Aim of this study was to evaluate the expressions of miRNA-21 and miRNA-18a in patients of ESCC and the effect of chemoradiotherapy (CRT) on expression of these miRNAs. METHODS: This was a case-control study conducted from September 2014 to December 2015 at Sri Aurobindo Medical College and Postgraduate Institute, Indore, India. We compared the expression of miRNA-21 and miRNA-18a in 30 ESCC patients and 30 healthy controls using TaqMan probe-based quantitative real-time polymerase chain reaction (qRT-PCR) and changes in the expression in 16 patients of ESCC, who completed CRT. RESULTS: Both miRNA-21 and miRNA-18a had significantly higher levels of expression in ESCC patients than healthy controls (95% confidence interval (CI): 5.73 - 34.79; P < 0.002 and 95% CI: 3,361.36 - 6,744.23; P < 0.001), respectively. Receiver operating characteristic (ROC) curve analysis showed that combination of serum miRNA-18a and miRNA-21 overexpression could efficiently distinguish patients of ESCC from healthy controls. The miRNA-21 expression positively correlated with tumor invasion (P < 0.004), lymphatic metastasis (P < 0.011), distant metastasis (P < 0.038), and tumor stage (P < 0.001); however, there was no such association observed with miRNA-18a. In the treatment phase (post-CRT), a significant reduction (P < 0.001) was observed in both miRNAs (73.4% in miRNA-18a and 81.02% in miRNA-21). CONCLUSIONS: Both miRNA-21 and miRNA-18a were highly overexpressed in patients of ESCC and their expressions changed significantly with CRT. These miRNAs may be useful tools for the diagnosis and assessment of treatment response in ESCC patients. Further studies will be needed to validate these findings using large number of patients.