Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma

Background MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). Material/Methods We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. Results Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P<0.001). The expression of miRNA-506 in the plasma was closely associated with lymph node status (P=0.004), TNM stage (P=0.031), and tumor length (P<0.001). According to ROC curves, the area under the curve for plasma miRNA-506 was 0.835, indicating statistical significance for ESCC diagnosis by plasma miRNA-506 (P<0.001). Kaplan-Meier analysis showed that patients with high miRNA-506 expression had significantly shorter survival time than those with low miRNA-506 expression. Cox regression analysis demonstrated that T stage, N stage, tumor length, and miRNA-506 expression levels were significantly correlated with prognosis in ESCC patients. Conclusions miRNA-506 can serve as an important molecular marker for diagnosis and prognostic prediction of ESCC.

[1]  W. Park,et al.  miR-506 Regulates Epithelial Mesenchymal Transition in Breast Cancer Cell Lines , 2013, PloS one.

[2]  L. De Cecco,et al.  Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients , 2011, Oncotarget.

[3]  E. Steyerberg,et al.  Comparison of the 6th and 7th Editions of the UICC-AJCC TNM Classification for Esophageal Cancer , 2012, Annals of Surgical Oncology.

[4]  Li Tian,et al.  miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1 , 2015, Oncotarget.

[5]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[6]  J. Chai,et al.  Esophageal malignancy: a growing concern. , 2012, World journal of gastroenterology.

[7]  Wei Zhang,et al.  MiR‐506 inhibits multiple targets in the epithelial‐to‐mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer , 2015, The Journal of pathology.

[8]  J. Mendell,et al.  MicroRNAs in Stress Signaling and Human Disease , 2012, Cell.

[9]  K. Mimori,et al.  The miR-506-Induced Epithelial–Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer , 2015, Annals of Surgical Oncology.

[10]  Qiang Feng,et al.  Identification of genomic alterations in oesophageal squamous cell cancer , 2014, Nature.

[11]  Christopher J. Cheng,et al.  MicroRNA silencing for cancer therapy targeted to the tumor microenvironment , 2014, Nature.

[12]  P. Khaitovich,et al.  Genomic analysis of miRNAs in an extreme mammalian hibernator, the Arctic ground squirrel. , 2010, Physiological genomics.

[13]  Ilya Shmulevich,et al.  MiR‐506 suppresses proliferation and induces senescence by directly targeting the CDK4/6–FOXM1 axis in ovarian cancer , 2014, The Journal of pathology.

[14]  Dabiao Liu.  LYN, a Key Gene From Bioinformatics Analysis, Contributes to Development and Progression of Esophageal Adenocarcinoma , 2015, Medical science monitor basic research.

[15]  Wei Zhang,et al.  MiR-506: A Multitasker in Suppression of the Epithelial-to-Mesenchymal Transition. , 2014, RNA & disease.

[16]  Ilya Shmulevich,et al.  Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. , 2013, Cancer cell.

[17]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.

[18]  Wei Zhu,et al.  A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth , 2012, Oncogene.

[19]  Zheli Xu,et al.  miR-506 regulates breast cancer cell metastasis by targeting IQGAP1. , 2015, International journal of oncology.

[20]  Shan Gao,et al.  MiR-506 suppresses liver cancer angiogenesis through targeting sphingosine kinase 1 (SPHK1) mRNA. , 2015, Biochemical and biophysical research communications.

[21]  J. Banales,et al.  Post-translational Regulation of the Type III Inositol 1,4,5-Trisphosphate Receptor by miRNA-506* , 2014, The Journal of Biological Chemistry.

[22]  Zhe Wang,et al.  Selective killing of lung cancer cells by miRNA-506 molecule through inhibiting NF-κB p65 to evoke reactive oxygen species generation and p53 activation , 2014, Oncogene.

[23]  Ying Wang,et al.  miR-506 Inhibits Epithelial-to-Mesenchymal Transition and Angiogenesis in Gastric Cancer. , 2015, The American journal of pathology.