目的 探讨采用生物信息学方法,构建胶质瘤患者瞬时受体电位(TRP)基因家族表达的预后模型并进行验证。方法 从UCSC Xena数据库的TCGA target GTEx数据集中,提取癌症基因组图谱(TCGA)数据库523例低级别胶质瘤,171例高级别胶质瘤及基因组织表达(GTEx)数据库中105例正常脑皮质的RNA测序数据,使用R语言评估胶质瘤样本和正常脑皮质中TRP基因家族的表达差异;使用Lasso回归模型分析并构建TRP基因家族预后模型,并在中国脑胶质瘤图谱数据库(CGGA)中对该模型的预后效能进行验证,同时对高低风险评分的亚组进行免疫浸润分析。结果 TRP基因家族在胶质瘤中存在广泛的异常表达且与胶质瘤患者预后相关,并建立TRP基因家族相关的预后模型,在TCGA训练集中该模型的1,3,5年曲线下面积(AUC)值均大于0.8,在CCGA验证集中该模型的1,3,5年AUC值均大于0.6,证实该模型具有较好的预测价值。免疫浸润分析提示高风险评分组中患者免疫活性较差。结论 采用TCGA数据库成功构建TRP基因家族的预后模型,可为判断胶质瘤患者预后及指导临床治疗提供帮助。
Abstract
Objective To construct a prognostic model of transient receptor potential (TRP) gene family in glioma patients with a bioinformatics approach and to determine its prognosis for glioma patients.Methods RNA sequencing data of 523 cases of low-grade glioma, 171 cases of high-grade glioma and 105 cases of normal cerebral cortex were extracted from the TCGA target GTEx datase of UCSC Xena database, and the different expression of TRP family in glioma samples and normal cerebral cortex were assessed with R language; Lasso regression model was used to analyze and construct a TRP family-related prognostic model. The prognostic efficacy of the model was validated in the CGGA database, and immune infiltration analysis was performed for subgroups with high and low risk scores.Results The prognostic model of TRP family was established, and the value of the area under the curve of the model were higher than 0.8 at 1, 3 and 5 years in the TCGA training set, and higher than 0.6 at 1, 3 and 5 years in the CCGA validation set, which confirmed the predictive value of the model. The immune infiltration analysis suggested that patients in the high-risk score group had poor immune activity.Conclusion The prognostic model of TRP gene family can be successfully constructedwith TCGA database, which can help to judge the prognosis of glioma patients and guide the clinical treatment.
关键词
瞬时受体电位基因家族 /
胶质瘤 /
预后模型 /
生物信息学 /
免疫微环境 /
基因组图谱
Key words
transient receptor potential family /
glioma /
prognostic model /
bioinformatics /
immune microenvironment /
the cancer genome atlas
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Reifenberger G, Wirsching H G, Knobbe-Thomsen C B, et al. Advances in the molecular genetics of gliomas-implications for classification and therapy[J]. Nat Rev Clin Oncol, 2017,14(7):434-452.
[2] Wesseling P, Capper D. WHO 2016 Classification of gliomas[J]. Neuropathol Appl Neurobiol, 2018,44(2):139-150.
[3] Nicholson J G, Fine H A. Diffuse glioma heterogeneity and its therapeutic implications[J]. Cancer Discov, 2021,11(3):575-590.
[4] Zhao Y, McVeigh B M, Moiseenkova-Bell V Y. Structural pharmacology of TRP channels[J]. J Mol Biol, 2021,433(17):166914.
[5] Moran M M. TRP channels as potential drug targets[J]. Annu Rev Pharmacol Toxicol, 2018,58:309-330.
[6] Zhao Z, Zhang K N, Wang Q, et al. Chinese Glioma Genome Atlas (CGGA):a comprehensive resource with functional genomic data from chinese glioma patients[J]. GPB, 2021,19(1):1-12.
[7] Engebretsen S, Bohlin J. Statistical predictions with glmnet[J]. Clin Epigenetics, 2019,11(1):123.
[8] Newman A M, Liu C L, Green M R, et al. Robust enumeration of cell subsets from tissue expression profiles[J]. Nat Methods, 2015,12(5):453-457.
[9] Oh D Y, Fong L. Cytotoxic CD4(+) T cells in cancer: expanding the immune effector toolbox[J]. Immunity, 2021,54(12):2701-2711.
[10] Thommen D S, Schumacher T N. T cell dysfunction in cancer[J]. Cancer Cell, 2018,33(4):547-562.
[11] Milici A, Talavera K. TRP channels as cellular targets of particulate matter[J]. Int J Mol Sci, 2021,22(5):478.
[12] Caterina M J, Schumacher M A, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway[J]. Nature, 1997,389(6653):816-824.
[13] Moore C, Gupta R, Jordt S E, et al. Regulation of pain and itch by TRP channels[J]. Neurosci Bull, 2018,34(1):120-142.
[14] Bomben V C, Sontheimer H W. Inhibition of transient receptor potential canonical channels impairs cytokinesis in human malignant gliomas[J]. Cell Prolif, 2008,41(1):98-121.
[15] Ji D, Luo Z W, Ovcjak A, et al. Role of TRPM2 in brain tumours and potential as a drug target[J]. Acta Pharmacol Sin, 2022,43(4):759-770.
[16] Zeng J, Wu Y, Zhuang S, et al. Identification of the role of TRPM8 in glioblastoma and its effect on proliferation, apoptosis and invasion of the U251 human glioblastoma cell line[J]. Oncol Rep, 2019,42(4):1517-1526.
[17] Morelli M B, Nabissi M, Amantini C, et al. The transient receptor potential vanilloid-2 cation channelimpairs glioblastoma stem-like cell proliferation and promotes differentiation[J]. Int J Cancer, 2012,131(7):E1067-E1077.
[18] 何 心, 秦至臻, 李 鑫, 等. 生物信息学分析影响胶质母细胞瘤生物学行为的关键基因[J]. 武警医学, 2020,31(4):328-331.
PDF(4848 KB)
