背景:细胞周期蛋白D1(CCND1)在细胞周期调节中起着至关重要的作用,并且与各种癌症有关。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,并旨在提供跨多种癌症类型的CCND1的全面分析。专注于它的表达,临床相关性,DNA甲基化状态,预后影响,遗传改变,和免疫浸润。
方法:使用TIMER对33种癌症类型进行了CCND1的基因表达分析,GEPIA,和UALCAN数据库。研究临床参数以评估其与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启动子甲基化与基因表达之间的关系及其与生存的关系。进行免疫浸润和存活分析以探索CCND1表达在各种癌症中的预后意义。统计检验,如Cox比例风险模型和Kaplan-Meier分析,用于评估生存结果。此外,我们使用cBioPortal数据库进行了基因改变分析,以检查不同癌症类型中CCND1改变的患病率和类型.
结果:与正常组织相比,CCND1在13种癌症中的表达显著升高,在不同的癌症类型中观察到不同的模式。它在BLCA中高度表达,CHOL,COAD,ESCA,GBM,HNSC,KIRC,PAAD,RRAD,READ,STAD,THCA,和UCEC。对临床参数的研究揭示了CCND1表达与年龄等因素之间的关联。性别,种族,和癌症阶段。甲基化分析强调了在13种选定的癌症类型中CCND1的低甲基化。生存分析确定了不同癌症中CCND1表达的有利和不利预后意义,并揭示了CCND1的高表达与HNSC和PAAD的不良预后相关。虽然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,在免疫细胞类型和肿瘤纯度之间观察到许多统计学上显著的相关性.例如,在BLCA,中性粒细胞和树突状细胞与巨噬细胞呈显著正相关,呈负相关.在CHOL患者中,免疫细胞类型均无显著相关性。在其他癌症类型中观察到类似的统计意义,比如COAD,HNSC,GBM,KIRC,PAAD,PRAD,READ,STAD,不同的免疫细胞类型。遗传改变分析显示,扩增是CCND1的主要遗传改变类型,在不同癌症类型中观察到特定模式。
结论:这项研究的发现为CCND1在癌症诊断和进展中的作用提供了有价值的见解。以及其靶向治疗的潜力。CCND1可以用作COAD的潜在诊断生物标志物,ESCA,KIRC,READ,STAD,和THCA阶段。此外,CCND1可作为HNSC的潜在预后生物标志物,KIRC,和PAAD。此外,CCND1甲基化与表达的相关性可作为ESCA的潜在诊断和预后标志物,HNSC,和STAD。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.