CCND1 作为预后和诊断生物标志物及其表观遗传改变对癌症生存的影响。
CCND1 as a Prognostic and Diagnostic Biomarker and the Impact of Its Epigenetic Alterations on Cancer Survival.
发表日期:2024 Jul
作者:
Muhammed Y Taha, Noha O Mohamed, Lina G Alhaj, Issra Altayeb, Abeer Basheer, Shaymaa Idrees, Abdirahman M Said, Mohamed Alfaki
来源:
Epigenetics & Chromatin
摘要:
细胞周期蛋白 D1 (CCND1) 在细胞周期调节中发挥着至关重要的作用,并与多种癌症有关。众所周知,癌症是由基因组中有害变异的积累引起的。在这项研究中,我们阐明了 CCND1 在癌症诊断和进展中的作用,旨在对多种癌症类型中的 CCND1 进行全面分析,重点关注其表达、临床相关性、DNA 甲基化状态、预后影响、遗传改变使用 TIMER、GEPIA 和 UALCAN 数据库对 33 种癌症类型进行 CCND1 基因表达分析。研究临床参数以评估它们与 CCND1 表达的相关性。使用 UALCAN 和 GSCA 数据库进行甲基化分析,以研究 CCND1 启动子甲基化和基因表达之间的关系及其与生存的关联。进行免疫浸润和生存分析,以探讨 CCND1 表达在各种癌症中的预后意义。使用 Cox 比例风险模型和 Kaplan-Meier 分析等统计检验来评估生存结果。此外,使用 cBioPortal 数据库进行遗传改变分析,以检查不同癌症类型中 CCND1 改变的患病率和类型。与正常组织相比,CCND1 表达在 13 种癌症中显着升高,在不同癌症类型中观察到不同的模式。它在 BLCA、CHOL、COAD、ESCA、GBM、HNSC、KIRC、PAAD、RRAD、READ、STAD、THCA 和 UCEC 中高度表达。临床参数的调查揭示了 CCND1 表达与年龄、性别、种族和癌症分期等因素之间的关联。甲基化分析强调了 CCND1 在 13 种选定癌症类型中的低甲基化。生存分析确定了 CCND1 表达在不同癌症中的有利和不利的预后影响,并揭示了 CCND1 的高表达与 HNSC 和 PAAD 的不良预后相关,而 CCND1 的高表达与 KIRC 的良好预后相关。 STAD、THCA 和 UCEC。在各种癌症的免疫浸润分析中,观察到免疫细胞类型和肿瘤纯度之间存在许多统计学上显着的相关性。例如,在 BLCA 中,中性粒细胞和树突状细胞显示出统计学上显着的正相关性,而与巨噬细胞则显示出显着的负相关性。而在 CHOL 患者中,没有一种免疫细胞类型显示出显着的相关性。在具有不同免疫细胞类型的其他癌症类型中也观察到类似的统计显着性,例如 COAD、HNSC、GBM、KIRC、PAAD、PRAD、READ 和 STAD。基因改变分析显示,扩增是 CCND1 中主要的基因改变类型,在不同的癌症类型中观察到特定的模式。这项研究的结果为了解 CCND1 在癌症诊断和进展中的作用及其靶向治疗的潜力提供了宝贵的见解。 。 CCND1 可用作 COAD、ESCA、KIRC、READ、STAD 和 THCA 阶段的潜在诊断生物标志物。此外,CCND1 可用作 HNSC、KIRC 和 PAAD 的潜在预后生物标志物。此外,CCND1 甲基化和表达之间的相关性可用作 ESCA、HNSC 和 STAD 的潜在诊断和预后生物标志物。版权所有 © 2024,Taha 等人。
Cyclin D1 (CCND1) plays a crucial role in cell cycle regulation and has been implicated in various cancers. As is well known, cancer is caused by the accumulation of detrimental variations in the genome. In this study, we shed light on the role of CCND1 in the diagnosis and progression of cancer and aimed to provide a comprehensive analysis of CCND1 across multiple cancer types, focusing on its expression, clinical correlations, DNA methylation status, prognostic implications, genetic alterations, and immune infiltration.Gene expression analysis of CCND1 was conducted across 33 cancer types using the TIMER, GEPIA, and UALCAN databases. Clinical parameters were investigated to assess their correlations with CCND1 expression. Methylation analysis was performed using the UALCAN and GSCA databases to investigate the relationship between CCND1 promoter methylation and gene expression and their association with survival. Immune infiltration and survival analyses were performed to explore the prognostic implications of CCND1 expression in various cancers. Statistical tests, such as the Cox proportional hazards model and the Kaplan-Meier analysis, were used to assess survival outcomes. Additionally, genetic alteration analysis was performed using the cBioPortal database to examine the prevalence and types of CCND1 alterations across different cancer types.CCND1 expression was significantly elevated in 13 cancers compared to normal tissues, with distinct patterns observed across different cancer types. It is highly expressed in BLCA, CHOL, COAD, ESCA, GBM, HNSC, KIRC, PAAD, RRAD, READ, STAD, THCA, and UCEC. The investigation of clinical parameters revealed associations between CCND1 expression and factors such as age, gender, race, and cancer stage. The methylation analysis highlighted hypomethylation of CCND1 across the 13 selected cancer types. The survival analysis identified both favorable and unfavorable prognostic implications of CCND1 expression in different cancers and revealed that a high expression of CCND1 was associated with a poor prognosis in HNSC and PAAD, while a high expression of CCND1 was associated with a good prognosis in KIRC, STAD, THCA, and UCEC. In the immune infiltration analysis of various cancers, many statistically significant correlations were observed between the immune cell types and tumor purity. For example, in BLCA, neutrophils and dendritic cells showed statistically significant positive correlations and a negative correlation with macrophages. While in CHOL patients, none of the immune cell types showed a significant correlation. Similar statistical significance was observed in other cancer types, such as COAD, HNSC, GBM, KIRC, PAAD, PRAD, READ, and STAD, with different immune cell types. The genetic alteration analysis revealed that amplification was the predominant genetic alteration type in CCND1, with specific patterns observed in different cancer types.The findings of this study provide valuable insights into the role of CCND1 in cancer diagnosis and progression, and its potential for targeted therapies. CCND1 could be used as a potential diagnostic biomarker for the COAD, ESCA, KIRC, READ, STAD, and THCA stages. Furthermore, CCND1 could be used as a potential prognostic biomarker for HNSC, KIRC, and PAAD. Also, the correlation between CCND1 methylation and expression could be used as a potential diagnostic and prognostic biomarker for ESCA, HNSC, and STAD.Copyright © 2024, Taha et al.