Chen Wenli, Cheng Xing, Wang Xiaobo, Wang Jinshan, Wen Xiaoling, Xie Chaofan, Liao Chuangxin
Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
Oncol Lett. 2019 Mar;17(3):2867-2873. doi: 10.3892/ol.2019.9929. Epub 2019 Jan 14.
Glioblastoma multiforme (GBM) is the most common type of primary brain tumour in adults, and presents a very low survival rate. Isocitrate dehydrogenase (IDH)1/2 mutations have been found in ~12% of glioblastomas and are associated with long-term GBM survival. However, the risk factors that influence the prognosis of IDH-wild type GBM remain unclear. Hypoxia-inducible factor (HIF)-1α, an important oxygen-regulated transcription factor, has been demonstrated to serve a crucial role in tumour development and to be associated with a poor prognosis. In addition, caveolin-1 (CAV1) is a plasma membrane organizing protein, the expression of which can also be regulated by a hypoxic microenvironment. The present study therefore aimed to examine the expression levels of HIF-1α and CAV1, and their association with GBM prognosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyse the expression levels of HIF-1α and CAV1 in paired GBM tumour and adjacent non-tumour tissues. Immunohistochemistry was used to analyse the expression of the two proteins in paraffin-embedded tissues obtained from 42 patients with IDH-wild type GBM. Statistical analyses were performed to examine the correlation between HIF-1α and CAV1 expression and patient prognosis. The results revealed hat the expression levels of HIF-1α and CAV1 were upregulated in IDH-wild type GBM tissues compared to their paired non-tumour tissues (P<0.001). The expression of CAV1 was significantly correlated with high HIF-1α expression (P<0.01). In addition, overexpression of HIF-1α and CAV1 was markedly associated with a poor prognosis (P<0.001). In conclusion, HIF-1α and CAV1 may represent potential biomarkers for IDH-wild type GBM prognosis and potential targets for the development of therapies extending GBM survival.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤类型，生存率极低。在约12%的胶质母细胞瘤中发现了异柠檬酸脱氢酶（IDH）1/2突变，且这些突变与GBM的长期生存相关。然而，影响IDH野生型GBM预后的危险因素仍不清楚。缺氧诱导因子（HIF）-1α是一种重要的氧调节转录因子，已被证明在肿瘤发展中起关键作用，并与预后不良相关。此外，小窝蛋白-1（CAV1）是一种质膜组织蛋白，其表达也可受缺氧微环境调节。因此，本研究旨在检测HIF-1α和CAV1的表达水平及其与GBM预后的关系。采用逆转录定量聚合酶链反应和蛋白质印迹法分析HIF-1α和CAV1在配对的GBM肿瘤组织和相邻非肿瘤组织中的表达水平。免疫组织化学用于分析42例IDH野生型GBM患者石蜡包埋组织中这两种蛋白的表达。进行统计学分析以检验HIF-1α和CAV1表达与患者预后之间的相关性。结果显示，与配对的非肿瘤组织相比，IDH野生型GBM组织中HIF-1α和CAV1的表达水平上调（P<0.001）。CAV1的表达与HIF-1α的高表达显著相关（P<0.01）。此外，HIF-1α和CAV1的过表达与预后不良显著相关（P<0.001）。总之，HIF-1α和CAV1可能代表IDH野生型GBM预后的潜在生物标志物以及延长GBM生存期治疗开发的潜在靶点。
