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Identification of three m6A‐related mRNAs signature and risk score for the prognostication of hepatocellular carcinoma

机译:鉴定三个与m6A相关的mRNA签名和肝癌预后的风险评分

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摘要

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is extremely harmful to human health. In recent years, N6‐methyladenosine (m6A) RNA methylation in eukaryotic mRNA has been increasingly implicated in cancer pathogenesis and prognosis. In this study, we downloaded the expression profile and clinical information of 307 patients from The Cancer Genome Atlas database and 64 patients from the Gene Expression Omnibus (GEO) database, and univariate Cox analysis revealed that METTL14 was a prognostic m6A RNA methylation regulator. For further study on the related genes of METTL14, weighted gene co‐expression network analysis was used to find the relationship between METTL14 and gene expression, and univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) methods were used to identify hub genes that may be associated with HCC prognosis. The results indicated that cysteine sulfinic acid decarboxylase, glutamic‐oxaloacetic transaminase 2, and suppressor of cytokine signaling 2 were key genes affecting the prognosis of HCC patients, and m6A methylation of these mRNAs may be regulated by METTL14. Finally, a nomogram was constructed based on the hub gene expression levels, and its prediction accuracy and discriminative ability were measured by the C‐index and a calibration curve. In conclusion, METTL14, an m6A RNA methylation regulator, may participate in the malignant progression of HCC by adjusting the m6A of cysteine sulfinic acid decarboxylase, glutamic‐oxaloacetic transaminase 2, and suppressor of cytokine signaling 2, and these genes are useful for prognostic stratification and treatment strategy development.
机译:肝细胞癌(HCC)是最常见的肝癌类型,对人体健康极为有害。近年来,真核mRNA中的N6-甲基腺苷(m6A)RNA甲基化已越来越多地牵涉到癌症的发病机理和预后。在这项研究中,我们从The Cancer Genome Atlas数据库下载了307例患者的表达谱和临床信息,从Gene Expression Omnibus(GEO)数据库下载了64例患者,单变量Cox分析显示METTL14是一种预后的m6A RNA甲基化调节剂。为了进一步研究METTL14的相关基因,使用加权基因共表达网络分析法发现METTL14与基因表达之间的关系,并使用单变量Cox分析和最小绝对收缩与选择算子(LASSO)方法来鉴定轮毂基因。可能与HCC预后有关。结果表明,半胱氨酸亚磺酸脱羧酶,谷氨酸-草酰乙酸转氨酶2和细胞因子信号转导抑制因子2是影响HCC患者预后的关键基因,这些基因的m6A甲基化可能受METTL14调控。最后,基于集线器基因表达水平构建列线图,并通过C指数和校准曲线测量其预测准确性和判别能力。总之,METTL14是一种m6A RNA甲基化调节剂,可通过调节半胱氨酸亚磺酸脱羧酶,谷氨酸-草酰乙酸转氨酶2和细胞因子信号转导抑制剂2的m6A来参与HCC的恶性进展,这些基因可用于预后分层和治疗策略的制定。

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