| BackgroundEsophageal cancer is the eighth most common cancer in the world. In 2012 the number of new cases was 456,000 cases (all new tumors 3.2%),400,000 deaths due to esophageal cancer cases (4.9% of all cancer deaths), ranking No.6. China is a high incidence of esophageal cancer, the incidence of esophageal cancer ranks first in the world, Europe and other Western countries, the incidence of esophageal cancer patients are increasing year by year. A report in 2012 showed that China was 22.14 esophageal cancer/100,000, ranking No.5 all kinds of cancer; mortality rate was 16.77/100,000, ranking No.4. Since the early symptoms of esophageal cancer are more hidden, most of the patients are advanced cancer. Western countries, mainly in patients with esophageal cancer are esophageal adenocarcinoma, while in China and other Eastern countries more than 90% histological type are esophageal squamous cell carcinoma. In recent years, the development of surgery, chemotherapy and radiotherapy, the clinical treatment of esophageal cancer has been much progress, but the 5-year overall survival rate is still below 20%, But the advanced cancer of surgery alone 5-year survival rate is very low. The processes incidence of esophageal cancer development involved in the multi-factor priming, multi-stage, multiple genetic changes. Not only the impact of environmental factors, but also involves the activation of oncogenes and inactivation of tumor suppressor genes and cell cycle regulation and other factors, some molecular genetic changes. However, esophageal cancer gene mutation induced factors and biological mechanisms are not clear. Now, with the development of molecular biology to explore the progression of esophageal cancer gene level to explore the impact of laws and the development of molecular biology and prognosis of esophageal cancer substance marked a record in recent years, research has become a hot topic.HER-2/neu (C-erbB-2) as a proto-oncogene, Shih etc found in neuroblastoma ethylimino nitrate caused by rats in the early 80s of the last century, such genes often in the human fetus to express only low levels of expression in some tissues presented in adulthood. Human HER-2/neu gene is an important member of the EGFR family, HER family belongs to the type Ⅰ receptor tyrosine kinase, is a membrane-binding proteins, including Her-1 (EGFR), Her-2/neu, Her-3, Her-4, etc. Their molecular structure is very similar to a combination of different ligands with the extracellular ligand-binding domain occurred, will lead to a series of signal transduction cascade waterfall phenomenon, and thus affect the structure of the cell biology. They are mainly mediated by the growth, proliferation, differentiation, adhesion, motility, survival and homeostasis of other phenomena, play an important role in the regulation of cell proliferation and differentiation. The main mechanism of its family of ligand upon binding initiate cell growth cycle, so that the receptor of Tyrosine protein kinase (TPK) is activated, TPK activate the intracellular signal transduction system, signaling to the growth the nucleus, leading to DNA synthesis and stimulate cell growth and proliferation of various.Normally Her-2 is inactive, currently no known ligands, it needs to work together with other receptor binding. Her-2 proto-oncogene can plays a critical role in cell growth factor in signaling pathway, to promot cell division and the secretion of proteolytic enzymes, enhance the capacity of the cell’s transport and promote tumor invasion and metastasis, and tumor pathological mechanisms and development. It is closely related to the pathological mechanisms and development. Her-2/neu is possible to play the following roles in tumor genesis and development: ①Through the matrix metalloproteinases, (MMPs) play a catalytic role in the secretion, leaving the organization structure changes, so that the shift or transfer of tumor cells, and (or) play a catalytic role in tumor cell invasion and transfer; ②Vascular endothelial growth factor (VEGF) is currently the most clinically been found to induce tumor angiogenesis factor, HER-2/neu and VEGF promoter can be activated quickly, making it in the mRNA and protein levels skills enhancement; ③High expression of Her-2/neu in allows serine/threonine kinase (AKT) and nuclear factor-kB is activated quickly, making cancer cells to tumor necrosis factor-a (TNFa) an effective role in the resistance, reducing the host’s immunity to tumor cells; ④Through the PI3K/AKT transduction pathways for apoptosis is suppressed, and the cell cycle faster. In recent years, studies found that high expression of Her-2 has been found in a variety of tumors, such as colorectal cancer, bladder cancer, ovarian cancer. Studies have shown that more than 30% of human tumor tissues with Her-2 overexpression, especially breast cancer whose overexpression was positively correlated with the degree of differentiation of breast cancer, clinical stage was, and is, the higher the expression, the worse the prognosisIt is not clear that whether Her-2 is the risks associated with esophageal cancer, whether it is an indicator of poor prognosis of esophageal cancer. There are two different views about Her-2 relationship with esophageal cancer survival:One view is that the two are closely related, but another point of view there was no significant correlation. Previous studies collected were analyzed in order to get a more definitive conclusion on whether Herceptin have a chance to become the targeted drugs in treatment of patients with esophageal cancerObjectiveMany researchers have studied the human epidermal growth factor receptor 2 (Her-2) expression correlated with esophageal cancer, and use it to determine the prognosis of esophageal cancer, but whether the Her-2 may be the prognosis of esophageal cancer is still controversial. To collect domestic and foreign literature about the clinical significance in patients with esophageal cancer tissue expression of Her-2, and through the Meta analysis compares patients with esophageal cancer tissue expression of Her-2 positive and negative, and look for whether there are any clinical significance between them. To study whether the patients who express Her-2 positive the 5-year survival shorter than the negative’s. Aims to systematicall evaluate the relationship between the expression of Her-2 in esophageal cancer and the biological behaviour of occurrence and development of esophageal cancer, and look forward to provide a new method for the Comprehensive treatment of esophageal cancer, a mean for to judge the esophageal cancer biology behavior, a approach for the targeted therapy of esophageal cancer.Methods1. Set out inclusion and exclusion critera for analysis according to the requests of Meta-analysis, including the characteristics of the subjects, detection methods and measure indexes.2. Retrospective cohort study which relevant of the expression and clinical significance in esophageal cancer in (1990.1-2014.9) were retrieved by computerized searching from Pubmed, EMbase, Cochrane Library, CNKI Library, CBM, Wangfang Database, VIP and those in Chinese Conference Treatises and graduate thesis. Using the way of the combination of subject terms and freewords, all retrieval strategy determined after times retrieval. Literature in the Internet using search engine such as Google, and auxiliary with hand search and literature back.3. Two reviewers independently extracted the information of the included studies. In the event of difference through discussion or by the third researchers to work out. Material extraction content including:(1) the basic condition of the experiment, (2) the detection and examine methods of the experimental, the measurement index of results, and the prognosis of research.4. Material statistical processing:Use the Stata 11.0 to perform the meta-analysis. Dichotomous data were calculated as Odds ratio (OR) and 95% Confidence interval (CI). The heterogeneity between the studies was detected using chi-square test, to a=0.1 for inspection standards, to judge the population effect of the results of the study are consistent.If no heterogeneity was detected between included trials, a fixed-effect model was used meta-analysis. Conversely, the random effects model be used. For to perform the different ethnic that may influence the results studied for sensitivity analysis, and to judge the stability and strength of results.5. the publication bias analysis and the susceptivity analysis was also evaluated to make sure the results stable.Results1. Description of studiesA total of 20 studies were included into the review. All the trials included a total of 3185 cases of esophageal cancer patients, including the expression or amplification of the Her-2 was 872 cases, and Her-2 negative patients for 2313 cases, The studies included 16 papers in English,4 papers in Chinese,10 papers studied and analyzed the Asian populations.The histological type of esophageal cancer include 8 articles esophageal squamous cell carcinoma and 7 articles adenocarcinoma of the esophagus.8 studies using immunohistochemical staining to detect the expression of Her-2,5 studies using fluorescence in situ hybridization,7 studies used more than two kinds of methods to detect.2. Meta-analysis results2.1 Her-2 expression in esophageal cancer patients compares with positive and negative in 5-year survival.20 researches on Meta-analysis, and heterogeneous inspection, (Chi2=25.91, P=0.13, I2=27%), using fixed effects model. The result shows that OR=0.59,95%CI:(0.48,0.73), P< 0.00001. Suggesting that the expression of Her-2 in esophageal cancer patients 5-year survival rates were statistically significant differences.2.2 Her-2 expression in esophageal squamous cell carcinoma compares with positive and negative in 5-year survival.8 researches on Meta-analysis, and heterogeneous inspection, (P=0.28,12=18%), using fixed effects model. The result shows that OR=0.55,95%CI:(0.40,0.76), P=0.0003. Suggesting that the expression of Her-2 in esophageal squamous cell carcinoma 5-year survival rates were statistically significant differences.2.3 Her-2 expression in adenocarcinoma of the esophagus compares with positive and negative in 5-year survival.8 researches on Meta-analysis, and heterogeneous inspection, (P=0.39,I2=5%), using fixed effects model. The result shows that OR=0.55,95%CI:(0.29,0.72), P=0.0009. Suggesting that the expression of Her-2 in adenocarcinoma of the esophagus 5-year survival rates were statistically significant differences.ConclusionsThe expression of Her-2-positive in esophageal cancer patients has a shorter survival than the negative one, stratified analysis of different tissue types, suggesting that both the histological type is esophageal squamous cell carcinoma and adenocarcinoma of the esophagus, Her-2 expression have shorter 5-year survival, Describe the expression of the Her-2 patients reduces 5-year overall survival, and the expression of the Her-2 is the higher risk of esophageal cancer occur, is a marker of poor prognosis in esophageal cancer. So the expression of Her-2 can be a new direction for the future treatment of esophageal cancer, provides new means to determine the biological behavior of esophageal cancer, opened a new way for targeted therapy of esophageal cancer. |
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