Construction and validation of a novel prognostic model for lung squamous cell cancer based on N6-methyladenosine-related genes.
Construction and validation of a novel prognostic model for lung squamous cell cancer based on N6-methyladenosine-related genes.
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DOI：
10.1186/s12957-022-02509-1
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发表时间：
2022-02-27
影响因子：
3.2
通讯作者：
Xue J
中科院分区：
文献类型：
--
作者：
Jia E;Ren N;Guo B;Cui Z;Zhang B;Xue J
N6-甲基腺苷 (m6A) 是生物过程中最常见的 mRNA 修饰，与各种恶性肿瘤的发生和进展相关。本研究旨在构建基于 m6A 相关基因（受 m6A 调节剂影响的下游基因）的 LUSC 预后风险模型。基于 TCGA，我们将 m6A 调节剂基因改变和不改变的 LUSC 患者分为改变组和未改变组。使用单变量 Cox 和 Lasso 回归分析，我们确定了预后 m6A 相关基因，以构建预后风险模型。然后，我们应用多元 Cox 比例回归模型和生存分析来评估风险模型。此外，我们还绘制了受试者工作特征曲线，以评估基于 TCGA 和 GSE43131 的预后模型的效率。我们通过CIBERSORT方法分析了LUSC中肿瘤相关免疫细胞浸润的特征。三个 m6A 相关基因（FAM71F1、MT1E 和 MYEOV）被确定为 LUSC 的预后基因。构建了基于三个 m6A 相关基因的新型预后风险模型。多变量Cox分析显示，预后风险模型是独立危险因素（HR = 2.44，95% CI = 1.21~3.56，p = 0.029）。高危组患者的 TCGA (p = 0.018) 和 GSE43131 (p = 0.00017) 总生存率均较差。 TCGA中1、2、3年AUC值分别为0.662、0.662、0.655； GSE43131 的 1 年、2 年和 3 年 AUC 值分别为 0.724、0.724 和 0.722。高风险组中浸润的中性粒细胞比例高于低风险组（p = 0.028），而静息 NK 细胞比例（p = 0.002）较低。本研究生成了一种基于 LUSC 的三个 m6A 相关基因的新型预后风险模型。在线版本包含可在 10.1186/s12957-022-02509-1 获取的补充材料。
N6-methyladenosine (m6A) is the most prevalent modification in mRNA in biological processes and associated with various malignant tumor initiation and progression. The present study aimed to construct a prognostic risk model based on m6A-related genes (the downstream genes influenced by m6A modulators) for LUSC. Based on TCGA, we stratified LUSC patients with and without genetic alteration of m6A modulators into altered and unaltered groups. Using univariate Cox and Lasso regression analyses, we identified prognostic m6A-related genes to construct a prognostic risk model. We then applied a multivariate Cox proportional regression model and the survival analysis to evaluate the risk model. Moreover, we performed the Receiver operating characteristic curve to assess the efficiency of the prognostic model based on TCGA and GSE43131. We analyzed the characteristics of tumor-associated immune cell infiltration in LUSC through the CIBERSORT method. Three m6A-related genes (FAM71F1, MT1E, and MYEOV) were identified as prognostic genes for LUSC. A novel prognostic risk model based on the three m6A-related genes was constructed. The multivariate Cox analysis showed that the prognostic risk model was an independent risk factor (HR = 2.44, 95% CI = 1.21~3.56, p = 0.029). Patients with a high-risk group had worse overall survival both in TCGA (p = 0.018) and GSE43131 (p = 0.00017). The 1, 2, and 3-year AUC value in TCGA was 0.662, 0.662, and 0.655, respectively; The 1, 2, and 3-year AUC value in GSE43131 was 0.724, 0.724, and 0.722, respectively. The proportion of infiltrated neutrophils in the high-risk group was higher than that in the low-risk group (p = 0.028), whereas that of resting NK cells (p = 0.002) was lower. A novel prognostic risk model based on three m6A-related genes for LUSC was generated in this study. The online version contains supplementary material available at 10.1186/s12957-022-02509-1.
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