中心粒蛋白 Q 与肝细胞癌诊断和预后的相关性
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摘要
简介肝细胞癌（HCC）是肝癌的主要类型之一。以往的研究表明，中心粒蛋白家族与 HCC 增殖等恶性生物学行为有关。作为中心粒蛋白家族的一员，中心粒蛋白 Q（CENPQ）与各种肿瘤的免疫治疗和免疫细胞浸润密切相关。然而，CENPQ在HCC中的作用和机制仍不清楚：方法：利用多个公共数据库和 RT-qPCR 研究 CENPQ 在 HCC 中的表达。基于 TCGA 数据，分析了 CENPQ 与 HCC 患者临床病理特征和预后的相关性，并评估了其诊断价值。通过对差异表达基因的功能富集分析，探讨了CENPQ在HCC中的潜在生物学功能。利用单样本GSEA评估了肿瘤浸润免疫细胞类型的分布，并利用Spearman相关性分析了免疫检查点基因的表达。随后进行了功能缺失实验，以确定CENPQ对体外HCC细胞周期和增殖的功能：结果：CENPQ在HCC中高表达，并与体重、体重指数、年龄、甲胎蛋白、T期、病理分期、组织学分级和凝血酶原时间相关（均为p <0.05）。ROC和Kaplan-Meier分析表明，CENPQ有可能被用作HCC的诊断标志物（AUC = 0.881），其上调与OS（p = 0.002）、DSS（p < 0.001）和PFI（p = 0.002）的降低相关。功能富集分析表明，CENPQ 与 HCC 中的免疫细胞浸润、细胞周期和 hippo-merlin 信号转导失调等生物学过程有关。此外，CENPQ被敲除后，HCC细胞会出现G0/1期周期停滞和增殖能力下降：结论：CENPQ在HCC组织中的表达高于正常肝组织。结论：CENPQ 在 HCC 组织中的表达高于正常肝组织，与预后不良、免疫细胞浸润、细胞周期和增殖密切相关。因此，CENPQ可能成为HCC患者的一种有希望的预后生物标志物。关键词：中心粒蛋白Q；生物标志物；免疫浸润；细胞周期；肝细胞癌本文章由计算机程序翻译，如有差异，请以英文原文为准。
The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma
Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear.
Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro.
Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity.
Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.
Keywords: centromere protein Q, biomarker, immune infiltration, cell cycle, hepatocellular carcinoma
Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro.
Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity.
Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.
Keywords: centromere protein Q, biomarker, immune infiltration, cell cycle, hepatocellular carcinoma
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