鉴定 MCM4 作为肝细胞癌的预后标志物。
Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.
机构信息
Department of Radiotherapy, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
Department of Central Laboratory, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
出版信息
Biomed Res Int. 2021 Dec 18;2021:7479326. doi: 10.1155/2021/7479326. eCollection 2021.
METHODS
MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort.
RESULTS
It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUC = 0.9461, AUC = 0.7056) and GEO (GSE19665: AUC = 0.8800, AUC = 0.5100; GSE64041 AUC = 0.8038, AUC = 0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC.
CONCLUSION
MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.
方法
从 TCGA 和 GEO 数据中分析 HCC 中 MCM4 的表达差异，并通过实时 PCR 和 Western blot 进行验证。ROC 曲线用于分析 MCM4 和 AFP 的诊断价值。此外，还通过 UALCAN 网站观察 TCGA 队列中 MCM4 与 HCC 分期、淋巴结转移状态、分级或年龄的关系。通过单因素和多因素 Cox 分析和功能分析，探讨 MCM4 在 TCGA 队列中的预后价值。
结果
发现 MCM4 在 TCGA、GEO 和实验数据中的 HCC 组织中表达显著升高。此外，ROC 曲线分析表明，MCM4 作为诊断生物标志物优于 AFP（来自 TCGA 的 AUC = 0.9461，AUC = 0.7056 和来自 GEO 的 AUC = 0.8800，AUC = 0.5100；GSE64041 AUC = 0.8038，AUC = 0.6304）。60 对 HCC 及其相邻组织实时 PCR 结果中 MCM4 的 AUC 为 0.7172，表明 MCM4 具有预测价值。此外，从 UALCAN 网站观察到 MCM4 在不同分期、淋巴结转移状态、分级或年龄中的表达趋势不同。此外，多 ROC 分析显示，MCM4 作为生存预测因子在 1、3 和 5 年的优势更大，其 1 年、3 年和 5 年的 AUC 分别为 0.69、0.65 和 0.61。单因素和多因素 Cox 分析表明，MCM4 与 OS 独立相关。GSEA 显示，在 HCC 中，MCM4 与 CDC6、PLK1、CRC1 和 BUB1B 呈正相关，高度富集于 KEGG_CELL_CYCLE 信号通路。
结论
MCM4 可能是指导 HCC 患者预后状态的潜在生物标志物。
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