| Background:Malignant gliomas is the most common subtype of primary brain tumors, which is highly invasive and neurologically destructive tumors considered to carry an extremely high mortality rate. So far the conventional therapies is comprehensive trestment techniques based on surgery,but the recurrence rate of glioma is still quite high and overall prognosis is still poor,despite maximum treatment efforts,glioblastoma multiforme(GB),median survival ranges from12to15months,and the median lengths of survival is only5to10years for patients with diffuse astrocytoma (DA).With the dramatic progress made in pathogenesis and molecular mechanisms about malignant gliomas,geme therapy is being developed as a more effective strategy in treatment,and selecting proper tumor genes for targeted therapies has been always focused.The high mobility groupAl(HMGA1) is a non-histone architectural nuclear factor,which can modulate transcription by altering chromatin.Many previous analyses of HMGA1in Glioma, lung cancer, ovarian serous adenocarcinoma, liver cancer and other malignant epithelial tumors are abnormal expression, and is closely related to the degree of malignancy.However,the role of HMGA1in tumor progression is still not clear.Trophoblast cell surface antigen2(TROP2) protein is a type I transmembrane glycoprotein which is invariably upregulated in tumors compared with corresponding normal tissues and predicts poor survival in a variety of cancer entities.Recent studies showed TROP2is associated with tumor development and progression in a variety of epithelial carcinomas, while its expression and role in gliomas have not been considered. This paper was divided into two parts:1.HMGA1expression is associated with time to recurrence in patients with glioblastoma multiforme.2.investigate TROP2expression in malignant gliomas with different World Health Organization (WHO) classification and its correlation with tumor proliferation and angiogenesis.The first part:HMGA1expression is associated with time to recurrence in patients with glioblastoma multiformeObjective:The aim of this study was to explore the difference in HMGA1expression between primary and recurrent glioblastoma multiforme (GBM), and to determine whether the dysregulation of HMGA1expression has a role in the malignant progression of GBM.Methods:Paired primary and recurrent GBM specimens from the same patient were evaluated using immunohistochemical analysis. The association between HMGA1expression and progression-free survival time (PFST) was analyzed.Results:There was a significant difference in HMGA1expression between primary and recurrent tumors (p=0.036), and patients with tumors expressing HMGA1at a higher level had a significantly shorter PFST (6.1months vs.11.5months; p=0.030).Conclusion:Our study indicates that recurrent GBM express HMGA1at a higher level and that HMGA1overexpression is associated with shorter PFST in patients with GBM. These findings suggest that HMGA1potentially has an important role in the treatment of GBM. The second part:TROP2expression and its correlation with tumor proliferation and angiogenesis in human gliomasObjective:The aim of the study was to investigate TROP2expression in malignant gliomas with different World Health Organization (WHO) classification and its correlation with tumor proliferation and angiogenesis.MethodsImmuohistochemistry was used to determine TROP2and Ki-67expression and microvessel density (MVD) in tumor specimens and normal brain tissues from69glioma patients and the relationship between TROP2and Ki-67and MVD was investigated.Results:Immunohistochemistry results showed that TROP2expression was found in59(85.5%) of the69tumor specimens, but no expression in normal brain tissues. Furthermore, TROP2expression is significantly higher in WHO grade Ⅲ (P=0.025) and WHO grade Ⅳ(P=0.011) gliomas than in WHO grade Ⅱ gliomas. TROP2expression correlates with Ki-67(r=0.676, P=0.012) and MVD(r=0.365, P=0.035), but not with gender or age in human gliomas.Conclusion:These results suggested that TROP2correlated with malignancy, proliferation and angiogenesis in human gliomas. This is the first study describing TROP2expression in gliomas and its proliferation and angiogenesis-related characteristic may serve as a potential therapeutic target for glioma treatmen... |
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