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全基因组分析揭示了醇脱氢酶 1C 和分泌磷蛋白 1 是肺腺癌的预后生物标志物。

Genome-wide analysis reveals alcohol dehydrogenase 1C and secreted phosphoprotein 1 for prognostic biomarkers in lung adenocarcinoma.

机构信息

Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

出版信息

J Cell Physiol. 2019 Dec;234(12):22311-22320. doi: 10.1002/jcp.28797. Epub 2019 May 9.

Abstract

To seek out novel promising biomarkers for predicting lung adenocarcinoma (LUAD) prognosis, we conducted this study. First, 279 upregulated and 37 downregulated differentially expressed genes were obtained from LUAD and para-carcinoma tissues by the Affymetrix GeneChip Human Transcriptome Array. Then, we randomly classified samples of LUAD data set GSE31210 as training and testing sets in a 1:1 ratio. Alcohol dehydrogenase 1C (ADH1C) and secreted phosphoprotein 1 (SPP1) were finally identified correlating with the LUAD survival through least absolute shrinkage and selection operator penalized Cox proportion hazards regression model, and applied to build a 2-gene signature related to prognosis in training set. Univariate and multivariable survival analyses suggested that overall survival (OS) and relapse-free survival (RFS) in the 2-gene signature low-risk group were better than the high-risk group. Kaplan-Meier curves proved that elevated ADH1C expression and reduced SPP1 expression were related to better OS and RFS. Besides, the SPP1 expressed higher in LUAD than para-carcinoma tissues using quantitative reverse transcription polymerase chain reaction assay. Finally, the association between the two genes and clinicopathological parameters in 80 LUAD were analyzed, it is suggested that SPP1 was relevant to epidermal growth factor receptor mutation. These findings indicated that ADH1C and SPP1 might be novel promising biomarkers for predicting LUAD prognosis.

摘要

为了寻找预测肺腺癌 (LUAD) 预后的新型有前途的生物标志物,我们进行了这项研究。首先,通过 Affymetrix GeneChip Human Transcriptome Array 从 LUAD 和癌旁组织中获得了 279 个上调和 37 个下调的差异表达基因。然后,我们以 1:1 的比例随机将 LUAD 数据集 GSE31210 的样本分类为训练集和测试集。最后,通过最小绝对收缩和选择算子惩罚 Cox 比例风险回归模型,确定与 LUAD 生存相关的 ADH1C 和 SPP1,应用于构建与训练集预后相关的 2 基因标志物。单因素和多因素生存分析表明,低风险组的总生存 (OS) 和无复发生存 (RFS) 优于高风险组。Kaplan-Meier 曲线证明 ADH1C 表达升高和 SPP1 表达降低与更好的 OS 和 RFS 相关。此外,通过定量逆转录聚合酶链反应测定,发现 SPP1 在 LUAD 中的表达高于癌旁组织。最后,分析了 80 例 LUAD 中这两个基因与临床病理参数的关系,结果表明 SPP1 与表皮生长因子受体突变相关。这些发现表明 ADH1C 和 SPP1 可能是预测 LUAD 预后的新型有前途的生物标志物。

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