Study On The Expression Of HIF-1α And VEGF In Human Gliomas

Gliomas are the most common primary brain tumors. Although combined therapy including operation, radiotherapy and chemotherapy is available currently, the prognosis of patients with malignant gliomas is still very poor. With the increase of knowledge in tumor biology and molecular genetics, it has been verified that alteration of multiple genes is involved in the molecular pathogenesis and the development of gliomas just like other tumors in the other site of the body. Now, angiogenesis in the tumor has become one of the foremost topics of interest in biomedical research. It has been estimated that solid tumors couldn't grow larger than 1 to 2 mm~3 without forming new blood vessels (angiogenesis). Hypoxia inducible factor-1 (HIF-1) and VEGF plays a critical role in angiogenesis during vascular development in the rumors. Our study is to investigate the expressions of HIF-1a and VEGF in human gliomas.From sep.2004 to may.2005, we collected 37 samples of human gliomas and 4 samples of normal brain tissues from the patients, who received the operation in General Hospital and Huan Hu Hospital. The first part of this study was focused on the HIF-la expression in the samples. The RT-PCR and immunohistochemistry was applied to detect the expression of mRNA and protein respectively. The relationship between HIF-1a expression level and the glioma grades were analyzed. In the second part, the same methods were used to study the expression of VEGF in the same samples.As shown in the present study, the expression levels of HIF-la and VEGF was increased corresponding to the ascending of the glioma grades. In the normal brain tissues, the expression of HIF-la mRNA was detected by RT-PCR study, while theprotein expression of HIF-la wasn't detected by immunohistochemistry. At the same time, both VEGF mRNA and protein expression were detected in the normal tissues. Both of HIF-la and VEGF expression in higher grade gliomas were higher than those in the lower grade ones.The level of HIF-la mRNA (HIF-la mRNA/p-actin mRNA) was 0.25±0.07 in normal brain tissue, 0.32±0.15 in glioma grade I -II, 0.72±0.13 in grade III, 0.95±0.17 in grade IV. The HIF-la positive cell ration of glioma grade I -II, III, IV was 30.6%, 80% andl00% respectively. The differences of HIF-la expression levels between the lower-grade and higher-grade tumors were statistically significant (PO.05). The expression of HIF-la was positively correlated with the glioma grades at both mRNA and protein level (mRNA r=0.862, P<0.05;protein r=0.796, PO.05).VEGF mRNA expressed null in the normal brain tissue. The level of VEGF mRNA (VEGF mRNA^-actin mRNA) was 0.27±0.15 in glioma grade I-II, 0.62±0.07 in grade III, 0.96±0.21 in grade IV. The VEGF positive cell ration of glioma grade I -II, III, IV was 38.5%, 80% and 100% respectively. The differences of VEGF expression levels between the lower grade and higher grade tumors were statistically significant (P<0.05). The expression of VEGF was also positively correlated with the glioma grades at both mRNA and protein levels (mRNA r=0.735, PO.05;protein r=0.842, PO.05).The expression of HIF-la was also positively correlated with VEGF expression at both mRNA and protein levels (mRNA r=0.738, P<0.05;protein r=0.847, P<0.05). HIF-la and VEGF may play a critical role in the malignant progression of the gliomas regarding their role in angiogenesis. It also suggests they may be two candidate targets for the glioma therapy. Their definitive effects in the treatment of malignant gliomas would be studied further, both in vivo and in vitro.