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CDCA基因家族在乳腺癌中的作用。

Roles of the CDCA gene family in breast carcinoma.

作者信息

Ding Wei, Han Wei, Shi Chun-Tao, Yao Li-Qian, Liang Zhi-Wei, Zhou Ming-Hui, Wang Hao-Nan

机构信息

Ultrasonic Department, Kunshan Women and Children's HealthCare Hospital, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, PR China.

Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, PR China.

出版信息

Sci Prog. 2025 Jan-Mar;108(1):368504241312305. doi: 10.1177/00368504241312305.

Abstract

Cell division cycle-associated (CDCA) genes are dysregulated in carcinomas. Our study aims to identify similarities and differences of the clinical roles of CDCAs in breast cancer (BRCA) and to explore their potential mechanisms. In GEPIA, compared to normal tissues, expressions of CDCAs were higher in BRCA and sub-types. In addition, CDCAs were significantly positively related to stages and predicted worse survival in BRCA. In CancerSEA, expression levels of most CDCAs were strongly positively related to cell cycle, DNA damage, DNA repair, and proliferation. In TIMER, CDCAs were linked with immune infiltration levels of BRCA, including Dendritic cell, B cell and so on, and were positively related to most of the common markers of immune cells, especially CD38 of B cell and IL12RB2 of Th1. In GeneMANIA, there were complex interactions and co-expression relationships between CDCAs and cell division-associated genes. In addition, CDCA1, CDCA3, CDCA5, CDCA6 and CDCA8 had a high proportion of amplification in BRCA, and CDCA1, CDCA2, CDCA5, CDCA7 and CDCA8 had high levels of body DNA methylation. Among 11 transcription factors possibly combining promoters of all CDCAs, FOXP3 and YY1 were significantly higher in BRCA in comparison to normal tissues, and both had a positive relationship with all CDCAs in GEPIA and IHC. In addition, silencing FOXP3 or YY1 decreased levels of CDCAs in MDA-MB-231. In summary, CDCAs have various similarities in clinical functions, functional states, immune infiltration, and mechanisms, and they may become novel potential biomarkers for BRCA.

摘要

细胞分裂周期相关(CDCA)基因在癌症中表达失调。我们的研究旨在确定CDCA基因在乳腺癌(BRCA)临床作用中的异同,并探索其潜在机制。在GEPIA中,与正常组织相比,CDCA基因在BRCA及其亚型中的表达更高。此外,CDCA基因与BRCA的分期显著正相关,并预测其预后较差。在CancerSEA中,大多数CDCA基因的表达水平与细胞周期、DNA损伤、DNA修复和增殖密切正相关。在TIMER中,CDCA基因与BRCA的免疫浸润水平相关,包括树突状细胞、B细胞等,并且与大多数免疫细胞的常见标志物呈正相关,尤其是B细胞的CD38和Th1细胞的IL12RB2。在GeneMANIA中,CDCA基因与细胞分裂相关基因之间存在复杂的相互作用和共表达关系。此外,CDCA1、CDCA3、CDCA5、CDCA6和CDCA8在BRCA中有较高比例的扩增,而CDCA1、CDCA2、CDCA5、CDCA7和CDCA8有较高水平的体DNA甲基化。在可能结合所有CDCA基因启动子的11种转录因子中,与正常组织相比,FOXP3和YY1在BRCA中的表达显著更高,并且在GEPIA和免疫组化中两者均与所有CDCA基因呈正相关。此外,沉默FOXP3或YY1会降低MDA-MB-231中CDCA基因的水平。总之,CDCA基因在临床功能、功能状态、免疫浸润和机制方面存在各种相似之处,它们可能成为BRCA新的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b35b/11736775/794f205f47b5/10.1177_00368504241312305-fig1.jpg

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