DNAJC10 correlates with tumor immune characteristics and predicts the prognosis of glioma patients.
DNAJC10 correlates with tumor immune characteristics and predicts the prognosis of glioma patients.
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DNAJC10与肿瘤免疫特征相关并预测胶质瘤患者的预后
DOI：
10.1042/bsr20212378
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发表时间：
2022-01-28
影响因子：
4
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Liu F;Tu Z;Liu J;Long X;Xiao B;Fang H;Huang K;Zhu X
摘要背景：DnaJ热休克蛋白家族（Hsp 40）成员C10（DNAJC 10）在肿瘤中的作用已有报道，但其在胶质瘤中的作用尚不清楚。本研究揭示了DNAJC 10在胶质瘤中的预后作用和潜在功能。研究方法：使用逆转录和定量聚合酶链反应（RT-qPCR）来定量临床样品的相对DNAJC 10信使RNA（mRNA）表达。Western blot检测临床标本蛋白表达。采用Kaplan-Meier法（双侧对数秩检验）比较不同DNAJC 10表达水平胶质瘤患者的总生存期（OS）。单样本基因集富集分析（ssGSEA）用于估计免疫细胞浸润和免疫相关功能水平。通过单变量和多变量考克斯回归分析确定DNAJC 10的独立预后作用。使用R软件包'rms'使用多变量考克斯回归建立基于DNAJC 10的诺模图模型。结果如下：在神经胶质瘤中观察到较高的DNAJC 10，并且其在较高级别、异柠檬酸脱氢酶（IDH）-野生型、1 p/19 q非共缺失、O（6）-甲基鸟嘌呤-DNA甲基转移酶（MGMT）非甲基化神经胶质瘤中上调。与低DNAJC 10表达的胶质瘤相比，DNAJC 10高表达的胶质瘤预后较差。使用时间依赖性ROC模型发现DNA JC 10的1/3/5-OS的预测准确度是稳定且稳健的。富集分析认识到，T细胞活化和T细胞受体信号在较高DNAJC 10胶质瘤中富集。免疫/基质细胞浸润、肿瘤突变负荷（TMB）、拷贝数改变（CNA）负荷和免疫检查点基因（ICPGs）也与胶质瘤中DNAJC 10表达呈正相关。建立了基于DNAJ 10的诺模图模型，并显示出较强的预测能力。结论：DNAJC 10高表达与胶质瘤预后不良相关，是胶质瘤预后的潜在生物标志物。
Abstract Background: The role of DnaJ heat shock protein family (Hsp40) member C10 (DNAJC10) in cancers has been reported but its function in glioma is not clear. We reveal the prognostic role and underlying functions of DNAJC10 in glioma in the present study. Methods: Reverse Transcription and Quantitative Polymerase Chain Reaction (RT-qPCR) was used to quantify the relative DNAJC10 messenger RNA (mRNA) expression of clinical samples. Protein expressions of clinical samples were tested by Western blot. The overall survival (OS) of glioma patients with different DNAJC10 expression was compared by Kaplan–Meier method (two-sided log-rank test). Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the immune cell infiltrations and immune-related function levels. The independent prognostic role of DNAJC10 was determined by univariate and multivariate Cox regression analyses. The DNAJC10-based nomogram model was established using multivariate Cox regression by R package ‘rms’. Results: Higher DNAJC10 is observed in gliomas and it is up-regulated in higher grade, isocitrate dehydrogenase (IDH)-wild, 1p/19q non-codeletion, O(6)-methylguanine-DNA methyltransferase (MGMT) unmethylated gliomas. Gliomas with higher DNAJC10 expression present poorer prognosis compared with low-DNAJC10 gliomas. The predictive accuracy of 1/3/5-OS of DNAJC10 is found to be stable and robust using time-dependent ROC model. Enrichment analysis recognized that T-cell activation and T-cell receptor signaling were enriched in higher DNAJC10 gliomas. Immune/stromal cell infiltrations, tumor mutation burden (TMB), copy number alteration (CNA) burden and immune checkpoint genes (ICPGs) were also positively correlated with DNAJC10 expression in gliomas. DNAJ10-based nomogram model was established and showed strong prognosis-predictive ability. Conclusion: Higher DNAJC10 expression correlates with poor prognosis of glioma and it was a potential prognostic biomarker for glioma.