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Expression And Relationship Of USP22, MTA1and Ki-67in Esophageal Squamous Cell Carcinoma

Posted on:2015-11-30Degree:MasterType:Thesis
Country:ChinaCandidate:W F ZhengFull Text:PDF
GTID:2284330431992778Subject:Internal Medicine
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AimEsophageal cancer is a malignant tumor with high incidence and high mortality rate. In the word, its incidence is eighth, however its mortality is sixth. Specific molecular m-echanism of esophageal carcinoma occurrence is unclear. Using microarray technique,it has been found that more than100genes participate in the development of esophageal carcinoma. In recent years, it is found that ubiquitin specific peptidase22(USP22) is a new member of ubiquitin specific processing enzymes (UBPs) families.USP22gene lo-cates in chromosome17and contains1578base pairs that codes protein about60kda. USP22has an amino terminal of zinc finger motif which is the structure basis of mediat-ing USP22molecule interaction with the substrate target protein. USP22expresses in e-arly embryonic tissues, however in adult multiple tissues at different level, moderately in the heart and skeletal muscle, but weakly in the lung and the liver. The previous rese-arch results confirm that USP22is related to the occurrence of a wide variety of tumors and participates in the occurrence and development of tumors through front the embryos implantation, regulating cell cycle and telomerase dynamic balance, involving in signal transduction and transcription activation. In1993, a gene related to tumor metastasis ab-ility was found and isolated from the13762NF of rat breast cancer cells by Pencil, and it was the MTA1genes. Then it was found that MTA1gene locates on chromosome14 and its cDNA contains2756base pairs. MTA1protein is a subunit NuRD and has obvi-ous hydrophilic ability.Its amino acid sequence contains plenty of kinase phosphorylati-on sites.Many studies have shown that MTA1participates in the formation of tumors an-d progress through the way such as cell signal transduction, remodeling chromatin struc-ture, increasing or reducing expression of some genes related cancer. In1983, When Sc-holzen T and other people researched Hodgkin lymphoma cell line L428, they found a kind of nuclear antigen and named Ki-67with their school name. Ki-67gene locates on chromosome10. Ki-67protein relates to cell proliferation and can better reflect the prol-iferation activity of the cells. The study found that Ki-67protein is associated with the f-ormation, development and metastasis of tumor. At present, the joint detection the expr-ession of USP22、MTA1and Ki-67protein has not yet been reported in esophageal car-cinoma. By discussing USP22、MTA1and Ki-67protein expression in human esophage-al squamous carcinoma tissue, its relationship with tumor biological behavior and the c-orrelation between each other, this study may bring new prospects for early diagnosis of esophageal carcinoma patients, biological evaluation and molecular targeted therapy,etc.Materials and MethodsIn our hospital the first affiliated hospital of zhengzhou university, surgical removal specimens of44patients with esophageal carcinoma were collected from January2011to December2011. These specimens included carcinoma tissue, tissue adjacent to carci-noma(adjacent to carcinoma edge less than3cm) and normal tissues (adjacent to carcin-oma edge outside edge3cm). Before surgery, these patients had not received chemoradi-otherapy, traditional Chinese medicine and targeted therapy,etc, who were confirmed by pathology after surgery. The study included27cases of male,17cases of female. These patients aged45-82years old,≤6022cases,>6022cases; No lymph node metastasis (including local lymph node and distant lymph nodes)19cases,25cases of lymph node metastasis; Invasion full-layer(breakthrough muscle layer to outer membrane)23cases, not invasion full-luyer (not breakthrough muscle layer)21cases; Grade Ⅰ/Ⅰ-Ⅱ (high and high-moderate differentiation)15cases, grade Ⅱ (moderate differentiation)15cases, grade Ⅲ/Ⅱ and Ⅲ (low and moderate-low differentiation)14cases.Tested using SP immunohistochemical staining method, all test procedures strictly according to immunohistochemical test steps and their respective instruction.Used PBS buffer instead of a resistance as a negative control and a known positive breast biopsy as a positive control. SPSS17.0statistical software was used to analyze, the comparison of rates between groups using chi square test,correlation analysis using Spearman test, test level a=0.05.Results(1)Positive expression rate of USP22:normal group15.91%, tissue adjacent to car-cinoma36.36%, esophageal squamous cell carcinoma tissues68.18%. Any two compa-rison between the three groups was statistically significant (P<0.05). The positive expr-ession rate of USP22protein was associated with tumor invasion depth and histological grades, but it had nothing to do with lymph node metastasis, age and gender.(2)Positive expression rate of MTA1:normal group6.82%, tissue adjacent to carci-noma31.82%, esophageal squamous cell carcinoma tissues61.36%. Any two comparis-on between the three groups was statistically significant (P<0.05). The positive expres-sion rate of MTA1protein was significantly associated with lymph node metastasis, tu-mor invasion depth and histological grades, however it had nothing to do with age and gender.(3)Positive expression rate of Ki-67:normal group11.36%, tissue adjacent to carci-noma43.18%, esophageal squamous cell carcinoma tissues70.45%.Any two comparis-on between the three groups was statistically significant (P<0.05). Mostly cell nucleus is dyed and most positive cells are basal cells.The positive expression rate of Ki-67prot-ein was associated with lymph node metastasis, tumor invasion depth and histological grades, but it had nothing to do with age and gender.(4)In esophageal squamous cell carcinoma, the expression of USP22protein was positively correlated with the expression of MTA1protein. The expression of USP22protein was positively correlated with the expression of Ki-67protein. The expression of MTA1protein and the expression of Ki-67protein were uncorrelated.Conclusion(1)It is speculated that high expression of USP22protein may be involved in the development of esophageal carcinoma.(2) It hints MTA1protein is related to the occurrence of esophageal carcinoma and promotes the invasion and metastasis of tumor cells. (3)The ki-67protein is closely related to cell proliferation. It shows higher express-ion of Ki-67protein may be one mechanism of leading to esophageal carcinoma occur-ence and be significant to evaluate tumor cell proliferation status and research tumor biology behaviors.(4)This May indicate in the esophageal carcinoma, MTA1raises to activate the expression of USP22gene and makes USP22protein expressed high. USP22and Ki-67could both promote cell proliferation and tumor formation through some interation mechanism. USP22, MTA1and Ki-67proteins involve in the occurrence and developm-ent of esophageal carcinoma together. USP22,MTA1and Ki-67can be used as potential molecular markers. Joint detection can more accurately determine the biological behav-iors of esophageal carcinoma, which promotes the early diagnosis of esophageal carcin-oma and molecular targeted therapy.
Keywords/Search Tags:Esophageal squamous cell carcinoma, USP22, MTA1, Ki-67
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