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Study On The Expressions And Clinical Significance Of IER5Protein In The Digestive Systematic Carcinomas

Posted on:2013-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:J DuFull Text:PDF
GTID:2214330374458889Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The highest mortality of malignant tumor was found in china where about130millions of people died of carcinoma each year. The incidence of digestivesystematic carcinoma may be as high as60%in the malignant tumoroccurence. The total death rate of gastric carcinoma, hepatocellular carcinoma,colorectal carcinoma, esophageal carcinoma and pancreatic carcinoma wasabout60%in the patients who died of malignant tumors in both men andwomen. The occurrence of malignant tumors is related to the changes of somegenes. In physiological conditions, a dynamic balance between proliferationand apoptosis in epithelial cells is depended on the common regulation ofoncogenes, tumor suppressor genes and some of growth factors. Once thebalance is destroyed, that will lead to the abnormal cellular signal transductionand the breakup of cell cycle and differentiation mechanism. It will result inuncontrolled cell proliferation, blocked cell apoptosis and abnormal celldifferentiation. At last it will bring about the formation of tumors. With moreand more tumor related genes being found, exploring the pathogenesis oftumor at molecular level has become the hot spot in the tumor research fields.The genic diagnostics and acology provide a new method for mankind toovercome the malignant tumors.IER5gene (Immediate early response5) is one of the early responsegenes.The activation of early response genes is the first step reaction ofcell and chromosomes to external stimulations and play an important role inthe cell growth, cell cycle and apoptosis. Thus, the activation and regulation ofthese genes play an important role in cell growth control[1]. Foreign papersrevealed that IER5gene existed in some tumors and normal structure[2-4],associated with cell division and apoptosis. Our earlier studies showed:decreasing the expression of IER5gene can promote the proliferation of cervical carcinoma cells (Hela) and hepatocellular carcinoma cells (HepG2),inhibit cell apoptosis and impair cell radiation sensitivity; increasing theexpression of IER5gene can inhibit the proliferation of Hela and HepG2cells,promote cell apoptosis and improve the cell radiation sensitivity. The abovestudies indicate that in hepatocellular carcinoma and cervical cancer the IER5gene play an important role in the morbid development and the regulation ofradiation sensitivity. Its biological functions in radiative conditions areequivalent to tumor suppressor genes. The expressions and the exactbiological functions of IER5in the development of the digestive systematiccarcinomas have not been known. Therefore, we decided to adopt the westenblot and immunohistochemical methods to study the expression changes ofIER5in tumor tissues of esophageal squamous cell carcinoma, gastricadenocarcinoma, hepatocellular carcinoma and colorectal adenocarcinoma andto explore the role of IER5in these tumors occurrence and development.We expect to find a new molecular target for the diagnosis andtreatment of digestive systematic malignancies.Objective: We plan to study the expressions changes of IER5protein andits functions on the genesis and development in esophageal squamous cellcarcinoma, gastric adenocarcinoma, hepatocellular carcinoma and colorectaladenocarcinoma tissues by westen blot and immunohistochemistry methods.We expect to find a new target for the diagnosis and treatment of digestivesystematic carcinomas.Methods:1The IER5proteins were detected in respective20cases of esophagealsquamous cell carcinoma, gastric adenocarcinoma, hepatocellular carcinoma,colorectal adenocarcinoma and their corresponding distant normal tissues(from5cm at the tumor margin) by western blot methods.2The immunohistochemical SP method was used to detect the expression,localization and distribution situation of IER5protein in respective20cases ofesophageal squamous cell carcinoma, gastric adenocarcinoma, hepatocellularcarcinoma and colorectal adenocarcinoma and their corresponding distant normal tissues (from5cm at the tumor margin).3The conventional HE staining was detected the pathological category of thecancer and the corresponding distance normall tissues.Result:1The conventional HE staining showed that the tumor specimens accord withthe experimental requirements and the corresponding distant normal tissueshas not been tumor invasion (Fig.5-8).2The changes of IER5protein in esophageal squamous cell carcinoma, gastricadenocarcinoma, hepatocellular carcinoma and colorectal adenocarcinoma bywestern blot method: all specimens appeared specific expression strip ofIER5in32kD positions.2.1The IER5protein levels of esophageal squamous cell carcinoma tissues(0.498±0.054) were significantly higher than the corresponding distant normaltissues (0.201±0.025),(P<0.05)(Fig.1).2.2The IER5protein levels of gastric adenocarcinoma tissues (0.408±0.057)were significantly higher than the corresponding distant normal tissues(0.238±0.112),(P=0.003)(Fig.2).2.3The IER5protein levels of hepatocellular carcinoma tissues (0.769±0.101)were significantly higher than it in the corresponding distant normal tissues(0.283±0.134),(P=0.001)(Fig.3).2.4The IER5protein levels of colorectal adenocarcinoma tissues(0.487±0.112) were significantly higher than the corresponding distant normaltissues (0.249±0.096),(P<0.05)(Fig.4).2.5The IER5protein levels were difference among esophageal squamous cellcarcinoma, gastric adenocarcinoma, hepatocellular carcinoma and colorectaladenocarcinoma:the IER5protein levels of hepatocellular carcinoma werehigher than esophageal squamous cell carcinoma than colorectaladenocarcinoma than gastric adenocarcinoma,(P<0.05)(Fig.9).2.6The IER5protein levels were difference among distant normal esophageal,gastric, hepatocellular and colorectal tissues:the IER5protein levels of distantnormal hepatocellular tissues were higher than distant normal colorectal tissues than distant normal gastric tissues than distant normal esophagealtissues (P<0.05)(Fig.9).2.7The relationship between the IER5protein and the clinicopathologyfeatures of the digestive systematic carcinomaThe IER5protein levels of esophageal squamous cell carcinoma, gastricadenocarcinoma, hepatocellular carcinoma and colorectal adenocarcinomatissues were unrelated with age, gender, clinical staging and the lymph nodemetastasis status (P>0.05). The IER5protein levels of hepatocellularcarcinoma were unrelated with age, gender, tumor size, HBsAg, liver cirrhosis,clinical stage (P>0.05)(Table1-4).3The changes of IER5protein in tumour tissues by immunohistochemicalmethod: the IER5proteins were expressed in esophageal squamous cellcarcinoma, gastric adenocarcinoma, hepatocellular carcinoma, colorectaladenocarcinoma and corresponding distant normal tissues, mainly distributedin the cytoplasm, showing different shades of brown particles (Fig.5-8).3.1The IER5protein levels of esophageal squamous cell carcinoma tissues(0.049±0.008) were significantly higher than the corresponding distant normaltissues (0.019±0.002),(P<0.05)(Fig.5).3.2The IER5protein levels of gastric adenocarcinoma tissues (0.052±0.002)were significantly higher than the corresponding distant normal tissues(0.032±0.001),(P=0.036)(Fig.6).3.3The IER5protein levels of hepatocellular carcinoma tissues (0.064±0.014)were significantly higher than the corresponding distant normal tissues(0.035±0.001),(P=0.012)(Fig.7).3.4The IER5protein levels of colorectal adenocarcinoma tissues(0.057±0.009) were significantly higher than the corresponding distant normaltissues (0.033±0.015),(P=0.019)(Fig.8).3.5The IER5protein levels were difference among esophageal squamous cellcarcinoma, gastric adenocarcinoma, hepatocellular carcinoma and colorectaladenocarcinoma: The IER5protein levels of esophageal squamous cellcarcinoma were not different from gastric adenocarcinoma,(P>0.05); The IER5protein levels of hepatocellular carcinoma were higher than colorectaladenocarcinoma than gastric adenocarcinoma and esophageal squamous cellcarcinoma,(P<0.05)(Fig.10).3.6The IER5protein levels were not difference among distant normal gastric,hepatocellular and colorectal tissues,(P>0.05); The IER5protein levels ofdistant normal esophageal tissues were different from distant normal gastric,hepatocellular and colorectal tissues (P<0.05)(Fig.10).3.7The relationship between the expression levels of IER5protein andclinicopathology feature of the digestive systematic cacinomasThe expression of IER5protein in esophageal squamous cell carcinoma,gastric adenocarcinoma, hepatocellular carcinoma and colorectaladenocarcinoma tissues were unrelated with age, gender, clinical staging andthe lymph node metastasis (P>0.05). The IER5protein expression inhepatocellular carcinoma were unrelated with age, gender, tumor size, HBsAg,liver cirrhosis and clinical stage (P>0.05)(Table1-4).Conclusion:1The expressions of IER5protein increased significantly in esophagealsquamous cell carcinoma, gastric adenocarcinoma, heaptocellular carcinomaand colorectal adenocarcinoma tissues. And that the IER5protein levels ofhepatocellular carcinoma were highest among all kinds of carcinomas.2The expressions of IER5protein in esophageal squamous cell carcinoma,gastric adenocarcinoma, hepatocellular carcinoma and colorectaladenocarcinoma tissues were unrelated with age, gender, clinical staging andthe lymph node metastasis; the IER5protein expressions in hepatocellularcarcinoma were unrelated with age, gender, tumor size, HBsAg, liver cirrhosisand clinical stage.IER5protein may involved in the occurrence and development ofesophageal squamous cell carcinoma, gastric adenocarcinoma, hepatocellularcarcinoma and colorectal adenocarcinoma. We should expand the sample sizeto thoroughly study the relationship between IER5protein and the clinicalpathology features and the prognosis of some digestive systematic carcinomas to further explore the role of IER5as anticancer gene in occurrence anddevelopment of some digestive systematic tumors, especially thehepatocellular carcinoma. We expect to find a new target for diagnosis andtreatment of digestive systematic carcinomas, to improve the early diagnosisrate and perfect the prognosis and life quality of patients.
Keywords/Search Tags:IER5protein, Digestive systematic carcinoma, Proteinexpression, Immunologic imprint hybridization, Immunohistochemistry
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