m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor.
m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor.
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m6A RNA甲基化调节因子在睾丸生殖细胞肿瘤患者的预后中发挥重要作用
DOI：
10.21037/tau-20-963
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发表时间：
2021-03
影响因子：
2
通讯作者：
Song N
中科院分区：
文献类型：
--
作者：
Cong R;Ji C;Zhang J;Zhang Q;Zhou X;Yao L;Luan J;Meng X;Song N
研究发现n6 -甲基腺苷（m6A）在不同类型的癌症中与促进肿瘤发生有关，然而，m6A相关基因在睾丸生殖细胞肿瘤（TGCT）发展中的功能仍有待阐明。本研究旨在探讨m6A RNA甲基化调节因子在TGCT中的预后价值。方法从肿瘤基因组图谱（TCGA）数据库和基因型组织表达（GTEx）数据库中收集TGCT患者的临床病理参数和22个m6A调控基因的表达信息。我们分析了肿瘤组织与正常组织中m6A RNA甲基化调控因子的差异表达，以及m6A RNA甲基化调控因子的相关性。通过Cox单因素分析、LASSO (last absolute shrink and selection operator) Cox回归算法和Cox多因素比例风险回归分析，构建基于TCGA训练队列的风险评分，并在TCGA测试队列中进一步验证。然后，采用单因素和多因素Cox回归分析评估TGCT中风险评分与无进展生存期（PFS）之间的关系。最后，通过两个基因表达谱（GSE3218和GSE10783）作为独立的外部验证队列，进一步验证六基因风险评分。结果在TCGA和GTEx数据集中，TGCT组织中m6A调控基因的表达模式与正常组织不同。为了预测TGCT患者的预后，根据选定的6种m6A RNA甲基化调节因子（YTHDF1、RBM15、IGF2BP1、ZC3H13、METTL3和FMR1）计算风险评分。此外，我们发现高危组和低危组在血清标志物研究水平和组织学亚型上存在显著差异。单因素和多因素分析表明，高风险评分与不良PFS相关。最终，通过两个基因表达谱（GSE3218和GSE10783）进一步验证风险评分。基于选定的6个m6A RNA甲基化调控因子，我们建立了一个m6A甲基化相关风险评分，可以独立预测TGCT患者的预后，并验证了其在TCGA和GEO数据集上的预测效率。高危组患者与血清肿瘤标志物研究水平超过正常范围、非精原细胞瘤和不利的生存时间相关。然而，需要进一步的前瞻性实验来验证我们的结果。
Background N6-methyladenosine (m6A) is found to be associated with promoting tumorigenesis in different types of cancers, however, the function of m6A-related genes in testicular germ cell tumors (TGCT) development remains to be illuminated. This study aimed to investigated the prognostic value of m6A RNA methylation regulators in TGCT. Methods We collected TGCT patients’ information about clinicopathologic parameters and twenty-two m6A regulatory genes expression from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). We analyzed the differentially expressed m6A RNA methylation regulators between tumor tissues and normal tissues, as well as the correlation of m6A RNA methylation regulators. By using Cox univariate analysis, last absolute shrinkage and selection operator (LASSO) Cox regression algorithm and Cox multivariate proportional hazards regression analysis, a risk score was constructed based on a TCGA training cohort, and further verified in the TCGA testing cohort. Then, univariate and multivariate Cox regression analyses were used to evaluate the relationship between risk score and progression-free survival (PFS) in TGCT. Finally, the six-gene risk score was further verified by two gene expression profiles (GSE3218 and GSE10783) as an independent external validation cohort. Results Distinct expression patterns of m6A regulatory genes were identified between TGCT tissues and normal tissues in TCGA and GTEx datasets. To predict prognosis of TGCT patients, a risk score was calculated based on six selected m6A RNA methylation regulators (YTHDF1, RBM15, IGF2BP1, ZC3H13, METTL3, and FMR1). Additionally, we found significant differences between the high-risk and low-risk groups in serum marker study levels and histologic subtype. Univariate and multivariate analysis indicated that high risk score was associated with unfavorable PFS. Ultimately, the risk score was further verified by two gene expression profiles (GSE3218 and GSE10783). Conclusions Based on six selected m6A RNA methylation regulators, we developed a m6A methylation related risk score that can independently predict the prognosis of TGCT patients, and verify the prediction efficiency in TCGA and GEO datasets. Patients in high-risk group were associated with serum tumor marker study levels beyond the normal limits, non-seminoma, and unfavorable survival time. However, further prospective experiments should be carried out to verify our results.
影响因子：
3.8
作者：
Staibano S;Ilardi G;Leone V;Luise C;Merolla F;Esposito F;Morra F;Siano M;Franco R;Fusco A;Chieffi P;Celetti A
通讯作者：
Celetti A