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肝细胞癌切除术后患者的预后生物标志物鉴定。

Identification of prognostic biomarkers for patients with hepatocellular carcinoma after hepatectomy.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

出版信息

Oncol Rep. 2019 Mar;41(3):1586-1602. doi: 10.3892/or.2019.6953. Epub 2019 Jan 3.

DOI:10.3892/or.2019.6953
PMID:30628708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6365689/
Abstract

Hepatocellular carcinoma (HCC) is a lethal malignancy with high morbidity and mortality rates worldwide. The identification of prognosis‑associated biomarkers is crucial to improve HCC patient survival. The present study aimed to explore potential predictive biomarkers for HCC. Differentially expressed genes (DEGs) were analyzed in the GSE36376 dataset using GEO2R. Hub genes were identified and further investigated for prognostic value in HCC patients. A risk score model and nomogram were constructed to predict HCC prognosis using the prognosis‑associated genes and clinical factors. Pearson's correlation was employed to show interactions among hub genes. Gene enrichment analysis was performed to identify detailed biological processes and pathways. A total of 71 DEGs were obtained and seven (ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13, all adjusted P≤0.05) of the 10 hub genes were identified as prognosis‑related genes for survival analysis in HCC patients, including alcohol dehydrogenase 4 (class II), pi polypeptide (ADH4), cytochrome p450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 family 8 subfamily B member 1 (CYP8B1), solute carrier family 22 member 1 (SLC22A1), tyrosine aminotransferase (TAT) and hydroxysteroid 17‑β dehydrogenase 13 (HSD17B13). The risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The majority of genes showed significant Pearson's correlations with others (41 Pearson correlations P≤0.01, four Pearson correlations P>0.05). GO analysis revealed that terms such as 'chemical carcinogenesis' and 'drug metabolism‑cytochrome P450' were enriched and may prove helpful to elucidate the mechanisms of hepatocarcinogenesis. Hub genes ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13 may be useful as predictive biomarkers for HCC prognosis.

摘要

肝细胞癌 (HCC) 是一种具有高发病率和死亡率的致命恶性肿瘤。鉴定与预后相关的生物标志物对于改善 HCC 患者的生存至关重要。本研究旨在探索 HCC 的潜在预测生物标志物。使用 GEO2R 在 GSE36376 数据集分析差异表达基因 (DEGs)。鉴定并进一步研究 HCC 患者的预后价值。使用预后相关基因和临床因素构建风险评分模型和诺模图预测 HCC 预后。采用 Pearson 相关性显示基因之间的相互作用。进行基因富集分析以确定详细的生物学过程和途径。获得了 71 个 DEG，并鉴定出 10 个基因座中的 7 个 (ADH4、CYP2C8、CYP2C9、CYP8B1、SLC22A1、TAT 和 HSD17B13，均调整后 P≤0.05) 为与 HCC 患者生存分析相关的预后基因，包括醇脱氢酶 4 (II 类)、π 多肽 (ADH4)、细胞色素 P450 家族 2 亚家族 C 成员 8 (CYP2C8)、细胞色素 P450 家族 2 亚家族 C 成员 9 (CYP2C9)、细胞色素 P450 家族 8 亚家族 B 成员 1 (CYP8B1)、溶质载体家族 22 成员 1 (SLC22A1)、酪氨酸氨基转移酶 (TAT) 和羟甾类 17-β 脱氢酶 13 (HSD17B13)。风险评分模型可预测 HCC 预后，诺模图可视化了 HCC 预后的基因表达和临床因素概率。大多数基因与其他基因具有显著的 Pearson 相关性 (41 个 Pearson 相关性 P≤0.01，4 个 Pearson 相关性 P>0.05)。GO 分析显示，术语如“化学致癌作用”和“药物代谢-细胞色素 P450”等富集，可能有助于阐明肝癌发生的机制。基因座 ADH4、CYP2C8、CYP2C9、CYP8B1、SLC22A1、TAT 和 HSD17B13 可能可作为 HCC 预后的预测生物标志物。

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