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Expression Of ZEB1Protein And Its Correlation With Clinical Pathologic Factors In Osteosarcoma Patients

Posted on:2013-01-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:B YuFull Text:PDF
GTID:1114330374487836Subject:Surgery
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Background Since the1970s, survival in patients with high-grade osteosarcoma has improved from around15%to60%-70%. This improvement is generally attributed to the development of neo-adjuvant chemotherapy. The possibility of downgrading tumors before operation facilitated the evolution of reconstruction methods after tumor resection. Whereas up to the late seventies80%of patients with an extremity osteosarcoma ended up with an amputation. Nowadays limb saving surgery is possible in90%of patients. Decision making has become multifactorial with this. Some (especially biological) reconstruction methods, have excellent long term results but require a long rehabilitation time, whereas others, such as endo-prosthetic replacements, allow early mobilization but have problems in the long term. A reasonably accurate estimate of survival chance for patients early in treatment would be helpful in counseling patients and their parents and in therapeutic decision making. Choice and possible change of chemotherapy and of surgical approach could be tailored to the patient. Researchers have gradually realized that gene expression in osteosarcoma not only determines the tumorigenesis, progression, and prognosis of osteosarcoma but also affects the efficacy of the treatment for sarcoma. Gene therapy may be a promising approach to solve the problem of metastasis associated with osteosarcoma.The ZEB family of zinc finger transcription factors are essential players during normal embryonic development. One characteristic is that they induce epithelial to mesenchymal transition (EMT), a process that reorganizes epithelial cells to become migratory mesenchymal cells. E-cadherin is a major target gene of these transcriptional repressors, and this downregulation is considered a hallmark of EMT. In recent years, the involvement of the ZEB proteins in pathological contexts has been documented as well. Mutations in ZEB encoding genes cause severe syndromic malformations and evidence is mounting that links these factors to malignant tumor progression. The research on ZEB1will highlights its role in tumor malignancy. Objective To investigate the the expression of ZEB1in human osteosarcoma and Osteochondroma tissue. Methods The expression of ZEB1was evaluated by immunohistochemistry in paraffin-embedded tissues from56cases of osteosarcoma and56cases of osteoehondroma. Results The Positive rate of ZEB1in osteosarcoma was89.3%compared with33.9%in osteoehondroma. The ZEB1expression showed significant difference between osteosarcoma and osteoehondroma (P<0.01). Conclusion ZEB1was expressed significantly in osteosarcoma tissue. Objective To explore the possibility of ZEB1as the molecular target of osteosarcoma and lay the potent theoretical basis on diagnosis, prognosis evaluation and combined therapy design of osteosarcoma patients. Methods The relationship between ZEB1expressions and various clinicopathological factors was analyzed and the relationship between ZEBl expressions and the lifes spans of osteosarcoma patienis was retrospectively analyzed combined the linical follow-up data.Results The expression of ZEB1had no association with age,gender, pathological type, ennecking surgical stage and tumor location inosteosarcoma patients (P>0.05). The positive expression of ZEB1was correlated with enneking surgical staging, metastasis and recurrence. Its positive expression rate in enneking surgieal stage â… -stage â…¡A was significantly lower than that in stage â…¡ B-stage â…¢(P<0.05). The positive expression rate of ZEB1in non-metastasis and non-recurrence patients was significantly lower than that in patients with metastasis and recurrence (P<0.05). By follow up analysis, Patients with positive ZEB1expression had22.0months of median survival time, and The survival time had signifieant difference between Patienis with positive ZEB1 expression and those with negative ZEB1expression (P<0.05). The expressions of ZEB1protein, enneking surgieal stage, metastasis and recurrence were important factors affecting the survival time of osteosarcoma patienis(P value was0.015,0.035,0.012,0.024, respectively). Multifactor analysis showed that the positive expression of ZEB1protein and enneking surgieal stage were independent factors affecting the survival prognosis of osteosarcoma patienis(Pvalue was0.002and0.027, respectively). Conclusion Combined evaluation of ZEB1protein expression and clinical follow-up data analysis showed that ZEB1had close relationship with prognosis of osteosarcoma patients. ZEB1may as the important marker for judging prognosis of osteosarcoma. ZEB1may shed new light on the cancer therapy and become a beneficial supplement for osteosarcoma therapy.
Keywords/Search Tags:ZEB1, epithelial-to-mesenchymal transition, osteosarcoma, prognosis
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