Expression And Clinical Significance Of MiR-146a,miR-155in Human Esophageal Squamous Cell Carcinoma

Background and ObjectiveEsophageal cancer is the eighth most common form of malignancy worldwide, and is the sixth most common cause of cancer-related mortality. Despite advances in chemotherapy and surgical techniques, esophageal squamous cell carcinoma (ESCC) remains a highly aggressive malignancy with poor prognosis. The overall survival is less than10%, and the5-year survival rate after surgery is between20and40%.In the past several decades, cancer has been regarded as a complex genetic disease, and studies have focused on the malignant cell biology. The objective has been to identify the role of tumor suppressor genes and mutated oncogenes in cancer initiation, growth, invasion and metastasis.Micro-RNAs (miRNAs) are a class of non-coding endogenous small (22nt) RNAs. It has been estimated that about50%of miRNA genes are located in cancer-associated genomic regions or in fragile sites. It’s proposed that these miRNAs post-transcriptionally regulate gene function and may acts as oncogenes or tumor suppressor genes.miR-146a,miR-155may play an important role in physiological and pathological processes such as inflammation and immune responsiveness. The effects induced by miR-146a,miR-155are variable in different kinds of tumors. However, it is well demonstrated that miR-146a,miR-155actively participates in many vital biological procedures that contribute to tumor development, including the regulation of proliferation, apoptosis and metastasis. Accumulating evidence suggests that miRNAs are involved in the development of esophageal cancer. However, despite these advances the role and the detailed molecular mechanism of miR-146a,miR-155in the development of ESCC remain unclear.Materials and MethodsThe study included54patients with primary ESCC who underwent radical esophagectomy at the Henan Cancer Hospital (Zhengzhou, China), between2010and2012. None of the subjects had a previous history of cancer, metastatic disease and family history of cancer. Patients who had undergone preoperative radiotherapy, chemotherapy or biological therapy were excluded from the study.The tumor specimens were collected, avoiding areas of tumor necrosis, and the adjacent para-cancerous was obtained from an area>5cm away from the tumor. Fresh tissue specimens were stored in liquid nitrogen within30min after collection. They remained in liquid nitrogen at-80℃until the extraction of RNA.The cohort consisted of45men and7women. The median age at diagnosis was61years (range:45to82years). Forty patients had Stage Ⅰ or Ⅱ disease and14had Stage Ⅲ disease. Tumor differentiation grades and pTNM stages were classified according to the Union for International Cancer Control (UICC) TNM Classification of Carcinoma of Esophagus Primary Tumor.Statistical analysis was performed using SPSS software version16.0(SPSS Inc, USA). Two sample nonparametric tests were used to analyze differences between paired samples and the independent sample Mann-Whitney U test was used to assess the differences between non-normally distributed variables. Values of P<0.05were considered statistically significant.Results1)miR-146a expression was significantly higher in tumor tissue than in normal esophageal mucosa (Z=-2.563,P=0.011).2)The relative expression level was correlated with lymph node metastasis and pTNM stage (P<0.05). However, no significant associations were found between miR-146a in ESCC and depth of tumor invasion, degree of differentiation, smoking or drinking habit, age or gender(P>0.05). The relative expression of miR-146a in ESCC was lower in patients with lymph node metastasis than in patients without lymph node metastasis. It was also lower in tissues from tumors in late pTNM stage than in early stage tumor tissue samples.3)miR-155expression was significantly lower in tumor tissue than in normal esophageal mucosa (Z=-4.258,P=0.000).4)The relative expression level was correlated with lymph node metastasis (P <0.05). However, no significant associations were found between miR-155in ESCC and depth of tumor invasion, degree of differentiation, pTNM stage, smoking or drinking habit, age or gender(P>0.05).Conclusions1) The up-regulation of miR-146a may play a significant role in the initiation and progression of ESCC.2) The down-regulation of miR-155may play a significant role in the initiation and progression of ESCC.