Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma

Abstract

Background:Accumulating evidence indicates that dysregulated microRNA-146a (miR-146a) is involved in tumour genesis and cancer progression. We aimed to evaluate its expression level and the potential for the diagnosis and prognosis in oesophageal squamous cell cancer (ESCC).Methods:We examined miR-146a expression in 62 pairs of ESCC cancerous and matched paracancerous tissue, 115 formalin-fixed paraffin-embedded (FFPE) tissue samples and serum samples from 154 ESCC patients and 154 healthy volunteers using quantitative reverse transcription–PCR (qRT–PCR). Kaplan–Meier method, Cox regression and receiver-operating characteristic (ROC) curve analysis were applied to analyse its prognostic and diagnostic value.Results:MicroRNA-146a expression level was significantly decreased in ESCC tissue compared with paracancerous tissue (P<0.001). Its regulation level was negatively associated with T factor and TNM stage. Kaplan–Meier curve revealed that its downregulation level predicted worse overall survival (OS) and progression-free survival (PFS). Both univariate and multivariate analyses identified miR-146a expression as independent prognostic factor for OS and PFS. Serum miR-146a was significantly reduced in ESCC patients than in healthy controls (P<0.001). Area under the curve ROC value, sensitivity and specificity for this marker were 0.863±0.033, 85.7% and 68.6% in the Discovery Group, and 0.891±0.027, 82.1% and 83.3% in the Validation Group.Conclusions:MicroRNA-146a is significantly reduced in cancerous tissue and serum samples of ESCC patients. It is an ideal biomarker for the prognosis and diagnosis of ESCC.

miR-146a-5p mediates epithelial–mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2

“…Expression level of miR-146a-5p was downregulated in ESCC tissues compared with the adjacent normal tissues and it could predict overall survival (OS) and progression-free survival (PFS) of ESCC patients, which has been reported in our previous article (Wang et al , 2016a). The invasiveness of ESCC cells (EC 9706 and Eca 109) were examined after transfection.…”

“…In this way, miRNAs inhibit the expression of specific target genes (Pichler and Calin, 2015). Accumulating evidence has shown that miRNAs can participate in tumourigenesis, progression and metastasis either as oncogenes or tumour suppressors and have potential as diagnostic, prognostic and therapeutics factors in cancer medicine (Sita-Lumsden et al , 2013; Krzeszinski et al , 2014; Wang et al , 2016a). …”

“…On the other hand, it is upregulated in melanoma (Forloni et al , 2014), squamous cell carcinoma of the cervix (Wang et al , 2008) and thyroid carcinoma (Sun et al , 2015a). In our previous article, we found that miR-146a-5p level was significantly decreased in ESCC tissue and serum and it could act as a promising biomarker for the prognosis and diagnosis of ESCC (Wang et al , 2016a). In this study, we further investigated the mechanisms of miR-146a-5p in EMT progression of ESCC.…”

miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

“…They bind the 3’-untranslated region (UTR) of various target mRNAs, enhancing their degradation or their translational repression, leading to multiple biological consequences [5,6]. In several cancers, miR-146a (encoded on chromosome 5q33) is dysregulated and acts as an oncogene [7–9] or as a tumor-suppressor gene [10–14]. Meanwhile, Snail, an inducer of the epithelial to mesenchymal transition, induces miR-146a , stabilizing Wnt activity and attenuating tumorigenicity [15].…”

Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma

“…This observation is reflected by the global downregulation of miR-146 in ESCC tissues compared to tumor adjacent tissues, likely due to the effect of this negative feedback loop. 71 Even though, the oncogenic role of NF-κB is well known, NF-κB has also shown to activate miRNAs that possess both tumor-suppressive and tumor-promoting roles in a context-dependent manner. For instance, miR-31 has been shown to be a direct target of NF-κB in skin keratinocytes leading to hyperproliferation in psoriatic epidermis.…”