Identification of the Prognostic Signatures of Glioma With Different PTEN Status.
Identification of the Prognostic Signatures of Glioma With Different PTEN Status.
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不同 PTEN 状态的胶质瘤预后特征的鉴定
DOI：
10.3389/fonc.2021.633357
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发表时间：
2021
影响因子：
4.7
通讯作者：
Dong L
中科院分区：
文献类型：
--
作者：
Zhang P;Meng X;Liu L;Li S;Li Y;Ali S;Li S;Xiong J;Liu X;Li S;Xia Q;Dong L
高级别胶质瘤以细胞异质性、基因突变和预后差为特征。肿瘤抑制基因PTEN的缺失和突变（5%-40%）与胶质瘤患者的生存率和治疗耐药相关。胶质瘤中PTEN状态的独特预后分子特征的表征仍然不清楚。本研究建立了一种新的风险模型，筛选最佳预后标志，并计算不同PTEN状态的胶质瘤患者的风险评分。筛选结果显示，在PTEN-wt中有14个独立的预后基因标记，在-50 PTEN-mut亚组中有3个。此外，我们验证了风险评分作为一个独立的预后因素与肿瘤恶性程度显着相关。由于PTEN-mut胶质瘤的恶性度较高，我们探索了PTEN-mut胶质瘤中潜在治疗靶点的独立预后特征（CLCF 1、AEBP 1和OS 9）。我们进一步将IDH野生型胶质瘤患者分为GBM和LGG以验证治疗靶标沿着PTEN状态，值得注意的是，上述筛选的治疗靶标在IDH-wt/PTEN-mut GBM和LGG患者中也是重要的预后基因。我们进一步鉴定了小分子化合物（+）-JQ 1与所有三个靶点结合，表明PTEN-mut胶质瘤的潜在疗法。总之，新风险模型中的基因特征和风险评分有助于胶质瘤诊断、预后预测和治疗。
The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.
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影响因子：
--
作者：
Kessler T;Sahm F;Blaes J;Osswald M;Rübmann P;Milford D;Urban S;Jestaedt L;Heiland S;Bendszus M;Hertenstein A;Pfenning PN;Ruiz de Almodóvar C;Wick A;Winkler F;von Deimling A;Platten M;Wick W;Weiler M
通讯作者：
Weiler M
DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
4.1
作者：
Chang, Nakho;Ahn, Sun Hee;Nam, Do-Hyun
通讯作者：
Nam, Do-Hyun
影响因子：
16
作者：
Baek, JH;Mahon, PC;Semenza, GL
通讯作者：
Semenza, GL
影响因子：
15.9
作者：
Ichimura K;Pearson DM;Kocialkowski S;Bäcklund LM;Chan R;Jones DT;Collins VP
通讯作者：
Collins VP