A four-protein expression prognostic signature predicts clinical outcome of lower-grade glioma
A four-protein expression prognostic signature predicts clinical outcome of lower-grade glioma
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DOI：
10.1016/j.gene.2018.08.001
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发表时间：
2018-12-30
期刊：
影响因子：
3.5
通讯作者：
Mahalingam, Kulandaivelu
中科院分区：
文献类型：
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作者：
Patil, Vikas;Mahalingam, Kulandaivelu
背景：胶质瘤是一类起源于胶质细胞的脑肿瘤。低级别胶质瘤（LGG）包括世界卫生组织（WHO）II级和III级胶质瘤。由于LGG可浸润到邻近区域，肿瘤的完全切除是困难的，并且它导致复发和恶性进展为高级别胶质瘤。我们的研究揭示了LGG中强有力的生存指标，可以通过免疫组织化学检查来预测低级别的结局。此外，它解开了新的治疗目标，以提高生存的LGG patients.Methods：为了确定一个预后的签名的基础上，在LGGs的蛋白质表达，我们分析了反相蛋白质阵列数据的LGG样本（n = 380）从癌症基因组图谱队列。我们将样本随机分层为发现数据集（n = 228）和验证数据集（n = 152）。我们进行了多变量考克斯比例风险回归分析的蛋白质（n = 219）使用发现数据集与年龄，WHO分级和IDH突变status.Results：我们确定了四个蛋白质的预后签名，可以隔离成高风险和低风险的患者。在发现数据集（风险比[HR] = 4.11; 95%置信区间[CI] = 2.18-7.75; p < 0.0001）和验证数据集（HR = 3.49; 95% CI = 1.52-8.01; p < 0.0001）中，特征估计高风险患者的总体生存率较差。在四种标志物中，CHK2_pT68被发现具有保护性，而MSH 6、ARID 1A和PAXILLIN与较差的存活率相关。此外，多变量考克斯比例风险回归分析，这个签名与年龄，WHO分级和IDH突变状态显示，这个预后的签名是一个独立的criticator在这两个dataset.Conclusions：我们的发现发现了一组潜在的蛋白质生物标志物，以预测生存，这将有助于在随后的治疗管理LGG患者。
Background: Glioma is a wide category of brain tumor originates from glial cells. Lower-Grade Glioma (LGG) consists of World Health Organization (WHO) grade II and grade III gliomas. Since the LGGs can infiltrate into adjacent areas, the complete removal of tumor is difficult and it results in recurrence and malignant progression to high grade glioma. Our study uncovers robust survival indicators in LGG which can be checked by immunohistochemistry to predict the outcome of lower grade. In addition, it unravelled the novel therapeutic targets in order to improve the survival of LGG patients.Methods: To identify a prognostic signature based on protein expression in LGGs, we analysed Reverse Phase Protein Array data of LGG samples (n = 380) from The Cancer Genome Atlas cohort. We made random stratification of samples into discovery (n = 228) and validation datasets (n = 152). We performed multivariate Cox proportional hazards regression analysis of proteins (n = 219) using discovery dataset with age, WHO grade and IDH mutation status.Results: We identified four-protein prognostic signature that can segregate patients into high- and low-risk. The signature estimates poor overall survival for high-risk patients in both discovery (hazard ratio [HR] = 4.11; 95% confidence interval [CI] = 2.18-7.75; p < 0.0001) and validation datasets (HR = 3.49; 95% CI = 1.52-8.01; p < 0.0001). Among the four markers, CHK2_pT68 was found to be protective, while MSH6, ARID1A and PAXILLIN were associated with poor survival. Additionally, Multivariate Cox proportional hazards regression analysis of this signature with age, WHO grade and IDH mutation status revealed this prognostic signature to be an independent prognosticator in both datasets.Conclusions: Our finding discovered a set of potential protein biomarkers to predict survival and it will help in the subsequent treatment management of LGG patients.