| Background and ObjectiveCurrently, Esophageal carcinoma is one of the common malignant tumor in digestive system that have the characteristics of high incidence and high mortality, in which,the most common is esophageal squamous cell carcinoma, about90%. Each year about300000people die of this disease worldwide, China is a high incidence area of esophageal cancer in the world, about150000people died of this disease every year. As the early symptoms of esophageal cancer are not obvious and lack of early diagnosis methods, most patients are diagnosed at advanced stage. When diagnosed, the survival time of the majority of patients is less than one year, five year survival less than10%, but if we can early diagnose the disease and give the patient timely and effective treatment, the five year survival rate can reach more than90%. The treatment of the Esophageal cancer include surgery, radiotherapy, chemotherapy and biological therapy, In recent years, with the development of diagnosis methods and treatment technology of esophageal cancer, the survival rate and quality of life are improved, however, the overall treatment effective of esophageal cancer is still not satisfied. The development of esophageal cancer is usually experienced dysplasia, carcinoma in situ and invasive stages, but its pathogenesis remains unclear, like other malignancies, the complex evolutionary process involving multi-factor, multi-stage, mutation accumulation and interaction and it involves many changes in oncogenes, tumor suppressor genes and proteins at the molecular level. Therefore, to clarify the development mechanism of esophageal cancer will great help for the diagnosis and treatment of this disease.Programmed cell death, also called apoptosis, is induced by specific endogenous and exogenous signals which activated the cell death pathway and also regulated by many genes. Programmed cell death plays an important role in many biological processes, such as embryonic development, metamorphosis, normal tissue turnover. Any disorder of these processes can result in diseases or tumor development. Therefore, the genes involved in apoptosis can be used as the target genes for the treatment of cancer. PDCD4(Programmed cell death4) is a newly discovered tumor suppressor gene, recent studies show that it may become a potential anti-tumor therapeutic targets. PDCD4Initially has been found up-regulated in the process of apoptosis, but its specific role remains unclear. However, more and more evidence show that the expression level of PDCD4affect transcription, translation and regulates different signaling pathways and may become a tumor suppressor. Recent research data shows that the effect of PDCD4may be dependent on cell type or its genetic background. The current study found that PDCD4have the function of inhibition many tumors is expected to become a target protein for anti-tumor therapy.The adjacent normal tissue invasion and distant metastasis are important biological characteristics of malignant tumors. Invasion and metastasis have been known related with exotic expression of adhesion molecules. Epithelial cadherin (E-cadherin) is a calcium-dependent tansmembrane glycoprotein witch mediated homogeneous adhesion. E-cadherin can combine catenin molecule, such as a, β, y-catenin and P20to form a complex, which is important to its role. Expression of E-cadherin is regulate by a variety of proteins at different levels, the study found that E-cadherin is not only involved in the mediated intercellular adhesion and cell signal transduction, but also in tumor development when its gene expression is reduced or missing which weaken the connection between the cell and adhesion, involving in the invasion and metastasis of many tumor development. In this study, we use the Reverse Transcriptase-polymerase chain reaction(RT-PCR)method to detect the relative expression of PDCD4and E-cadherin in esophageal squamous cell carcinoma and adjacent normal tissue to Explore the mechanism of the two genes in the development of esophageal squamous cell carcinoma and its clinical significance, and provide new targets for the treatment of esophageal cancerMaterials and method1. All specimens of our research project are from the Second Affiliated Hospital of Zhengzhou University, Thoracic Surgery. From July2010to March2011,50cases of fresh esophageal squamous cell carcinoma tissues and corresponding adjacent normal tissues was collected (the normal tissues were more than5cm from the tumor edge). In which,31cases were male,19females; aged44～79years, mean57.8±7.52years; The UICC esophageal carcinoma of the TNM staging:I of9cases, Ⅱof23cases, Ⅲ of18cases, differentiation:highly and moderate differentiated in38cases, poorly differentiated in12cases;28cases did not invaded the esophageal fiber membrane,22cases invaded the esophageal fiber membrane and beyond,lymph node metastasis in37cases,13cases without lymph node metastasis;All patients had complete clinical data and esophageal squamous cell carcinoma were confirmed by pathological examination and no chemotherapy, radiotherapy and other anti-cancer treatment was used before the operation.2. The expression of two genes PDCD4and E-cadherin in52cases of esophageal squamous cell carcinoma and the adjacent normal tissue are detected by RT-PCR method. Combined with clinical and pathological festures in all cases, the relationship between PDCD4, E-cadherin and characteristics of clinical are analyzed.3. All statistical data were processed by statistical software SPSS17.0package, the means were expressed as x±s,comparison between the two groups of quantitative data was made by the t tests, t’test was used while the date does not meet the t test conditions. One-factor Analysis of Variance (one-way ANOVA) was used to compare the Quantitative data in multiple sets, comparison between groups by LSD-t test. The Pearson correlation was used to analyze PDCD4and E-cadherin expression. Statistically significant level was considered as "alpha equals0.05". Results1. The expression of PDCD4mRNA in esophageal squamous cell carcinoma was significantly lower than in adjacent normal esophageal tissues,(0.562±0.069vs1.134±0.122)(P<0.05)2. PDCD4mRNA in highly-moderately differentiated group was significantly higher than the poorly differentiated group (0.575±0.048vs0.526±0.032)(P<0.05) the expression in lymph node metastasis group is lower than those without lymph node metastasis (0.543±0.049vs0.586±0.073)(P<0.05); the expression PDCD4mRNA is related to the TNM staging of esophageal squamous cell carcinoma, the later stages,the lower expression, I:0.597±0.034Ⅱ:0.566±0.053Ⅲ:0.531±0.042(P<0.05). The expression of PDCD4mRNA has no obvious difference with Gender, age, invasion (P>0.05)3. The expression of E-cadherin mRNA in esophageal squamous cell carcinoma was significantly lower than the adjacent normal esophageal tissues,((0.186±0.0234vs0.481±0.03)(P<0.01)4. E-cadherin mRNA in highly-moderately differentiation group was significantly higher than the poorly differentiated group (0.199±0.024vs0.173±0.047)(P<0.05); the group which invaded the esophageal fiber membrane is lower than the the other group (0.170±0.038vs0.201±0.053)(P<0.05);22cases invaded the esophageal fiber membrane and beyond,.the expression in lymph node metastasis group is lower than those without lymph node metastasis(0.174±0.033vs0.208±0.025)(P<0.05); the expression of E-cadherin mRNA is related to the TNM staging of esophageal squamous cell carcinoma, the later stages,the lower expression,Ⅰ:0.215±0.032Ⅱ:0.183±0.029Ⅲ:0.152±0.021(P<0.05). The expression of PDCD4mRNA has no obvious difference with Gender, age (P>0.05)5. The expressions of PDCD4mRNA and E-cadherin mRNA in Carcinoma tissue both decreased, they have positive correlation, Pearson correlation coefficient: r=0.612(P<0.001).Conclusions1. The expression of PDCD4and E-cadherin in esophageal squamous cell carcinoma tissues was significantly lower than the adjacent normal esophageal tissue and they have positive correlation, implying they both involved in the occurrence of the cancer.2. In esophageal squamous cell carcinoma, the expression of PDCD4、 E-cadherin has no relationship with the patient gender, age, but with the cancer differentiation, lymph node metastasis, TNM staging, E-cadherin also have correlation with invasion of esophageal fiber membrane, implying they both involved in the development of the cancer.3. PDCD4、 E-cadherin may reflect the degree of malignancy of esophageal spuamous cell carcinoma, and are expected to become the target genes for diagnosis and therapy for esophageal squamous cell carcinoma. |
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