The Role of AHCY Expression in Bladder Urothelial Carcinoma: A Bioinformatics and Experimental Analysis.

IF 2.5 4区医学 Q3 ONCOLOGY

Cancer Management and Research Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI:10.2147/CMAR.S491044

Shaorui Niu, Xiaozhe Zheng, Yuyang Yao, Yue Dong, Yupan Hu, Zhiyang Xiao, Jiaxue Yang, Chengli Jiang, Xin Zou, Zihao Zou, Pang Yang

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引用次数: 0

Abstract

Background: Although adenosylhomocysteinase (AHCY) is crucial to the oncogenesis and growth of some cancers, it is unknown how this affects bladder urothelial carcinoma (BLCA). Investigating the variations in AHCY expression in BLCA and examining the relationship between AHCY expression and BLCA patient prognosis were the goals of this investigation.

Methods: By leveraging The Cancer Genome Atlas (TCGA) database, we undertook a meticulous examination of AHCY expression levels, juxtaposing them between BLCA and normal tissues. Subsequently, Kaplan-Meier analysis and COX regression and nomogram was used to assess the effect of AHCY on the survival of BLCA patients. We further elaborated on the possible enriched pathways of AHCY and its immune relevance. In addition, we employed si-RNA technology to downregulate the AHCY gene expression and subsequently utilized quantitative real-time PCR (qRT-PCR), CCK-8, cell scratch assays, and Transwell migration assays to validate the pivotal role of AHCY in BLCA.

Results: The expression of AHCY was associated with various types of malignancies (including BCLA). In BLCA cancer tissues, there was an observed upregulation of AHCY expression in comparison to paracancerous tissues. Increased expression of AHCY was linked to decreased overall survival (OS), clinical stage, N stage, and T stage in individuals with BLCA. The functional enrichment of AHCY related genes mainly involves biological processes such as rRNA metabolic processes, proteasome activity, and cell cycle regulation, etc. Furthermore, AHCY showed significant associations with m6A related genes and infiltration of immune cells (Especially for Th2 cells and T-gd lymphocytes). In vitro functional experiments substantiated that the inhibition of AHCY effectively suppresses the growth, migration, and invasion of bladder cancer cells.

Conclusion: This study provides novel insights into the role of AHCY in BLCA, which holds significant potential to contribute towards advancing the diagnosis and treatment of BLCA in the future.

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AHCY表达在膀胱尿路上皮癌中的作用：生物信息学和实验分析。

背景：虽然腺苷高半胱氨酸酶（AHCY）对某些癌症的发生和生长至关重要，但它如何影响膀胱尿路上皮癌（BLCA）尚不清楚。探讨AHCY在BLCA中的表达变化，探讨AHCY表达与BLCA患者预后的关系是本研究的目的。方法：利用癌症基因组图谱（TCGA）数据库，我们对AHCY表达水平进行了细致的检查，并将其在BLCA和正常组织之间进行了对比。随后，采用Kaplan-Meier分析和COX回归及nomogram分析AHCY对BLCA患者生存期的影响。我们进一步阐述了AHCY可能的富集途径及其免疫相关性。此外，我们采用si-RNA技术下调AHCY基因表达，随后利用实时荧光定量PCR （qRT-PCR）、CCK-8、细胞划痕实验和Transwell迁移实验验证AHCY在BLCA中的关键作用。结果：AHCY的表达与多种恶性肿瘤（包括BCLA）相关。在BLCA癌组织中，与癌旁组织相比，AHCY表达上调。AHCY表达的增加与BLCA患者总生存期（OS）、临床分期、N期和T期的降低有关。AHCY相关基因的功能富集主要涉及rRNA代谢过程、蛋白酶体活性、细胞周期调控等生物学过程。此外，AHCY与m6A相关基因和免疫细胞（特别是Th2细胞和T-gd淋巴细胞）浸润有显著相关性。体外功能实验证实，抑制AHCY可有效抑制膀胱癌细胞的生长、迁移和侵袭。结论：本研究为AHCY在BLCA中的作用提供了新的见解，这对未来BLCA的诊断和治疗具有重要的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.