LDHA is a prognostic biomarker on the immune response in pancreatic adenocarcinoma and associated with m6A modification
LDHA is a prognostic biomarker on the immune response in pancreatic adenocarcinoma and associated with m6A modification
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LDHA 是胰腺癌免疫反应的预后生物标志物，与 m6A 修饰相关
DOI：
10.1007/s00432-022-04400-8
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发表时间：
2022-10
影响因子：
3.6
通讯作者：
Chen Liang
中科院分区：
文献类型：
--
作者：
Zhen Tan;Jiang Liu;Jin Xu;Bo Zhang;Xianjun Yu;Wei Wang;Chen Liang
目的N6-甲基腺苷（m6A）与胰腺导管腺癌（PDAC）的进展密切相关。 PDAC的另一个显着特征是代谢重编程，它通过肿瘤微环境提供足够的营养来支持细胞的快速生长。然而，m6A 相关代谢基因对 PDAC 微环境的潜在影响仍知之甚少。因此，我们试图利用m6A相关基因构建生存预测模型，以阐明PDAC的分子特征。方法在本研究中，从癌症基因组图谱（TCGA）胰腺腺癌数据集中获得m6A相关代谢基因并进行共表达分析。根据 m6A 相关代谢基因的表达，共识聚类识别出具有不同免疫细胞浸润模式的两个不同亚组。采用多变量Cox回归分析和最小绝对收缩和选择算子（LASSO）分析来创建m6A相关代谢模型。构建了包含临床特征和基于 m6A 相关代谢调节因子表达的风险评分的列线图。结果构建了包含 ATP8B2、GMPS、LDHA 和 SDR39U1 的四基因特征来预测 PDAC 患者的总生存期 (OS)。该特征还有力地预测了来自国际癌症基因组联盟 (ICGC) 和 ArrayExpress (E-MTAB-6134) 的两个独立验证队列的生存率。四基因特征将患者分为高风险组和低风险组，并通过对数秩检验验证具有不同的 OS 值。在这四个基因中，LDHA 在 PDAC 组织和细胞系中均上调。结论总的来说，我们分析了免疫微环境，预测了药物敏感性，并根据 m6A 调节因子和代谢重连之间的串扰评估了突变景观的影响，并且我们还构建了基于 m6A 相关代谢基因的新特征来预测 PDAC 预后。
PurposeN6-methyladenosine (m6A) is tightly associated with the progression of pancreatic ductal adenocarcinoma (PDAC). Another prominent feature of PDAC is metabolic reprogramming, which provides sufficient nutrients to support rapid cell growth via the tumor microenvironment. However, the underlying influences of m6A-associated metabolic genes on the PDAC microenvironment remain poorly understood. Therefore, we sought to construct a survival prediction model using m6A-related genes to clarify the molecular characteristics of PDAC.MethodsIn the present study, m6A-related metabolic genes were obtained from The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma dataset and subjected to coexpression analysis. Consensus clustering recognized two distinct subgroups with different immune cell infiltration patterns according to the expression of m6A-associated metabolic genes. Multivariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO) analysis were adopted to create an m6A-related metabolism model. A nomogram including clinical features and the risk score based on the expression of m6A-related metabolism regulators was constructed.ResultsA four-gene signature comprising ATP8B2, GMPS, LDHA and SDR39U1 was built to predict the overall survival (OS) of PDAC patients. This signature also robustly predicted survival in two independent validation cohorts from the International Cancer Genome Consortium (ICGC) and ArrayExpress (E-MTAB-6134). The four-gene signature divided patients into high- and low-risk groups with distinct OS values as verified by the log-rank test. Among the four genes, LDHA was upregulated in both PDAC tissues and cell lines.ConclusionsCollectively, we analyzed the immune microenvironment, predicted drug sensitivity and assessed the implications of the mutation landscape based on the crosstalk between m6A regulators and metabolic rewiring, and we also constructed a novel signature based on m6A-associated metabolic genes to predict PDAC prognosis.
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DOI：
10.1016/j.omtn.2021.04.003
发表时间：
2021-06-04
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Xu F;Huang X;Li Y;Chen Y;Lin L
通讯作者：
Lin L
影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
DOI：
10.1016/j.respe.2020.09.004
发表时间：
2020-10-10
期刊：
Revue D'Epidemiologie et De Sante Publique
影响因子：
--
作者：
La rédaction
通讯作者：
La rédaction
影响因子：
9.3
作者：
通讯作者：
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