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缺氧诱导因子-1α(HIF-1α)和端粒酶逆转录酶(TERT)对胶质母细胞瘤患者生存结局的临床病理分析:一项前瞻性单机构研究

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study.

作者信息

Potharaju Mahadev, Mathavan Anugraha, Mangaleswaran Balamurugan, Patil Sushama, John Reginald, Ghosh Siddhartha, Kalavakonda Chandrasekhar, Ghosh Mitra, Verma Rama Shanker

机构信息

Department of Radiation Oncology, Apollo Speciality Hospitals, Chennai - 600035, India.

Department of Neurosurgery, Apollo Speciality Hospitals, Chennai - 600035, India.

出版信息

J Cancer. 2019 May 26;10(11):2397-2406. doi: 10.7150/jca.32909. eCollection 2019.

Abstract

Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 - 3.74, ). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the "HIF-1α - strong and TERT - strong" and the "HIF-1α - weak and TERT - weak" patient subgroups, as evaluated by Kaplan-Meier analysis (). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.

摘要

多形性胶质母细胞瘤是一种高度恶性且侵袭性强的原发性脑肿瘤,预后很差。我们研究了在接受标准治疗且随访充分的胶质母细胞瘤患者中,缺氧诱导因子-1α(HIF-1α)、端粒酶逆转录酶(TERT)、异柠檬酸脱氢酶1(IDH1)和肿瘤蛋白p53的免疫组化表达与总生存期(OS)之间的关联。在研究的87例患者样本中,59例为男性,28例为女性。中位年龄为55岁。中位随访时间为27.7个月,中位总生存期为14.9个月。所有样本均有HIF-1α的核染色,其中42例(48%)为强阳性,45例(52%)为弱阳性。多变量Cox回归显示,HIF-1α强表达是一个独立的不良预后因素(风险比2.12,95%置信区间1.20 - 3.74)。通过Kaplan-Meier分析评估,“HIF-1α强且TERT强”和“HIF-1α弱且TERT弱”患者亚组之间的总生存期存在统计学显著差异(9.

8个月对16.3个月)。在我们的研究中,HIF-1α表达是总生存期的独立预测因素。HIF-1α和TERT均强表达的患者亚组预后最差。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96f/6584346/50e26e9e9322/jcav10p2397g001.jpg

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