Identification of gene expression and DNA methylation of SERPINA5 and TIMP1 as novel prognostic markers in lower-grade gliomas
Identification of gene expression and DNA methylation of SERPINA5 and TIMP1 as novel prognostic markers in lower-grade gliomas
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鉴定 SERPINA5 和 TIMP1 的基因表达和 DNA 甲基化作为低级别胶质瘤的新型预后标志物
DOI：
10.7717/peerj.9262
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发表时间：
2020-06
期刊：
影响因子：
2.7
通讯作者：
Zhi-Cheng Gong
中科院分区：
文献类型：
--
作者：
Wen-Jing Zeng;Yong-Long Yang;Zhi-Peng Wen;Peng Chen;Xiao-Ping Chen;Zhi-Cheng Gong
背景：低级别胶质瘤（Lower-grade gliomas，LGGs）是一种特征性肿瘤，预后差异较大。由于预后生物标志物有限，迫切需要鉴定更多的分子标志物，以提供更客观和准确的LGG肿瘤分类系统。方法：在目前的研究中，我们对基因表达数据和全基因组甲基化数据进行了综合分析，以确定LGG中新的预后基因和甲基化位点。结果：筛选出44例短期存活者中差异表达的基因（SERPINA 5和TIMP 1）。Kaplan-Meier曲线显示SERPINA 5和TIMP 1表达与TCGA LGG患者的总生存期（OS）和无复发生存期（RFS）显著相关。我们接下来验证了CGGA LGG患者中候选基因表达与临床结果之间的相关性。多因素分析显示，TIMP 1 mRNA表达对预后的预测价值与其他因素无关（HR = 4.825，95% CI = 1.370-17.000，P=0.014）。然后，从差异候选基因表达组中鉴定差异甲基化位点，并且所有四个甲基化位点均与基因表达显著负相关（斯皮尔曼rP P SERPINA 5 cg 15509705（P = 0.0762）。结论：总之，这些发现表明SERPINA 5和TIMP 1的基因表达和甲基化可以作为LGG的预后预测因子，并可能有助于精确目前基于组织学的肿瘤分类系统，并为未来的临床试验提供更好的分层。
Background: Lower-grade gliomas (LGGs) is characteristic with great difference in prognosis. Due to limited prognostic biomarkers, it is urgent to identify more molecular markers to provide a more objective and accurate tumor classification system for LGGs..Methods：In the current study, we performed an integrated analysis of gene expression data and genome-wide methylation data to determine novel prognostic genes and methylation sites in LGGs..Results: To determine genes that differentially expressed between 44 short-term survivors (SERPINA5 and TIMP1 were selected for further study. Kaplan–Meier plots showed that SERPINA5 and TIMP1 expression were significantly correlated with overall survival (OS) and relapse-free survival (RFS) in TCGA LGGs patients. We next validated the correlation between the candidate genes expression and clinical outcome in CGGA LGGs patients. Multivariate analysis showed that TIMP1 mRNA expression had a significant prognostic value independent of other variables (HR = 4.825, 95% CI = 1.370–17.000, P=0.014). Then, differential methylation sites were identified from differentially candidate gene expression groups, and all four methylation sites were significantly negatively correlated with gene expression (spearman rP P SERPINA5 cg15509705 (P = 0.0762)..Conclusion: Taken together, these findings indicated that the gene expression and methylation of SERPINA5 and TIMP1 may serve as prognostic predictors in LGGs and may help to precise the current histology-based tumors classification system and to provide better stratification for future clinical trials.
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DOI：
10.1016/s1040-1741(10)79529-4
发表时间：
2010
期刊：
Yearbook of Oncology
影响因子：
--
作者：
R. Arceci
通讯作者：
R. Arceci
国际神经病理学协会 - 哈勒姆神经系统肿瘤分类和分级共识指南。
DOI：
10.1111/bpa.12171
发表时间：
2014-09
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Louis DN;Perry A;Burger P;Ellison DW;Reifenberger G;von Deimling A;Aldape K;Brat D;Collins VP;Eberhart C;Figarella-Branger D;Fuller GN;Giangaspero F;Giannini C;Hawkins C;Kleihues P;Korshunov A;Kros JM;Beatriz Lopes M;Ng HK;Ohgaki H;Paulus W;Pietsch T;Rosenblum M;Rushing E;Soylemezoglu F;Wiestler O;Wesseling P;International Society Of Neuropathology--Haarlem
通讯作者：
International Society Of Neuropathology--Haarlem
生物信息学分析鉴定胶质母细胞瘤与低级别胶质瘤差异表达关键基因
影响因子：
2.7
作者：
Xu, Yang;Geng, Rongxin;Chen, Qianxue
通讯作者：
Chen, Qianxue
影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
4.8
作者：
M. Crocker;B. Bell;S. Zacharoulis;M. Papadopoulos
通讯作者：
M. Crocker;B. Bell;S. Zacharoulis;M. Papadopoulos