An m6A-Related Prognostic Biomarker Associated With the Hepatocellular Carcinoma Immune Microenvironment.
An m6A-Related Prognostic Biomarker Associated With the Hepatocellular Carcinoma Immune Microenvironment.
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与肝细胞癌免疫微环境相关的 m6A 相关预后生物标志物
DOI：
10.3389/fphar.2021.707930
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发表时间：
2021
影响因子：
5.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Du Y;Ma Y;Zhu Q;Liu T;Jiao Y;Yuan P;Wang X
背景：n6 -甲基腺苷（m6A）与多种癌症的进展有关。然而，m6a相关基因对肝细胞癌（HCC）肿瘤免疫微环境的潜在影响尚不清楚。因此，我们试图构建一个使用m6a相关基因的生存预测模型，以阐明HCC的分子和免疫特性。方法：从癌症基因组图谱（TCGA）下载HCC病例数据。然后，通过应用共识聚类，我们确定了两个不同的HCC聚类。接下来，我们鉴定了4个m6a相关基因来构建预后模型，并使用Gene Expression Omnibus （GEO）和国际癌症基因组联盟（ICGC）数据集对其进行了验证。此外，还分析了不同亚组的分子和免疫特性。结果：m6A RNA甲基化调节因子在HCC和正常样本中表达差异，并与免疫检查点表达相关。采用共识聚类，我们将HCC样本分为两种具有不同临床特征的亚型。集群2与不良预后、较高的免疫检查点表达和免疫细胞浸润水平相关。此外，免疫和致癌信号通路在簇2中富集。此外，我们使用四个m6a相关基因构建了风险模型。不同风险评分的患者有不同的生存时间、免疫治疗生物标志物的表达水平、TP53突变率以及对化疗和靶向治疗的敏感性。同样，该模型在验证队列中对总生存率也有相同的影响。结论：构建的基于m6的信号可能是HCC预后和区分免疫特征的生物标志物。
Background: N6-methyladenosine (m6A) is related to the progression of multiple cancers. However, the underlying influences of m6A-associated genes on the tumor immune microenvironment in hepatocellular carcinoma (HCC) remain poorly understood. Therefore, we sought to construct a survival prediction model using m6A-associated genes to clarify the molecular and immune characteristics of HCC. Methods: HCC case data were downloaded from The Cancer Genome Atlas (TCGA). Then, by applying consensus clustering, we identified two distinct HCC clusters. Next, four m6A-related genes were identified to construct a prognostic model, which we validated with Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) datasets. Additionally, the molecular and immune characteristics in different subgroups were analyzed. Results: m6A RNA methylation regulators were differentially expressed between HCC and normal samples and linked with immune checkpoint expression. Using consensus clustering, we divided HCC samples into two subtypes with distinct clinical features. Cluster 2 was associated with unfavorable prognosis, higher immune checkpoint expression and immune cell infiltration levels. In addition, the immune and carcinogenic signaling pathways were enriched in cluster 2. Furthermore, we constructed a risk model using four m6A-associated genes. Patients with different risk scores had distinct survival times, expression levels of immunotherapy biomarkers, TP53 mutation rates, and sensitivities to chemotherapy and targeted therapy. Similarly, the model exhibited an identical impact on overall survival in the validation cohorts. Conclusion: The constructed m6A-based signature may be promising as a biomarker for prognostics and to distinguish immune characteristics in HCC.
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人类癌症中的 N6-甲基腺苷 (m6A) RNA 修饰
影响因子：
8.5
作者：
Huo FC;Zhu ZM;Pei DS
通讯作者：
Pei DS
影响因子：
51.1
作者：
Garassino, Marina C.;Gadgeel, Shirish;Rodriguez-Abreu, Delvys
通讯作者：
Rodriguez-Abreu, Delvys
影响因子：
6.8
作者：
He RZ;Jiang J;Luo DX
通讯作者：
Luo DX
PD1HiCD8 T 细胞与肝细胞癌的衰竭特征和不良临床结果相关
影响因子：
10.9
作者：
Jiaqiang;Zheng, Bohao;Zhang, Xiaoming
通讯作者：
Zhang, Xiaoming
DOI：
10.1016/j.omtn.2020.09.036
发表时间：
2020-12-04
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Liu X;Qin J;Gao T;Li C;He B;Pan B;Xu X;Chen X;Zeng K;Xu M;Zhu C;Pan Y;Sun H;Sun L;Xu T;Wang S
通讯作者：
Wang S