Expression pattern and prognostic significance of CDKs in breast cancer: An integrated bioinformatic study.

IF 1.9 4区 医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2022-04-25 DOI:10.3233/cbm-210186
Umar Mehraj, Shazia Sofi, B. Alshehri, M. A. Mir
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引用次数: 7

Abstract

BACKGROUND Globally, breast cancer (BC) has become one of the most prevalent malignancies and the leading cause of tumor-related deaths among women. Dysregulation of the cell cycle is a well-known hallmark of cancer development and metastasis. CDKs are essential components of the cell-cycle regulatory system with aberrant expression in a variety of cancers, including BC. In the development of targeted cancer treatment, reestablishing the regulation of the cell cycle by modulation of CDKs has emerged as a promising approach. METHODS Herein, we used a bioinformatic approach to assess the expression pattern, prognostic and diagnostic importance, and clinical relevance of CDKs in BC. Additionally, we conducted a functional enrichment analysis of deregulated CDKs using the STRING and KEGG databases to delineate the role of CDKs in breast tumorigenesis. RESULTS Gene expression analysis revealed substantial deregulation of CDKs in BC, with CDK1, CDK11A, and CDK18 showing a fold change of >± 1.5. Also, metastatic tumors showed high expression of CDK1 in the single cell RNA sequencing analysis of primary and metastatic breast tumors. Additionally, it was found that dysregulated CDK expression affects overall survival (OS) and relapse-free survival (RFS) of BC patients. CONCLUSION The study's multimodal analytical methodologies imply that modulating CDKs for BC treatment is a promising approach.
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CDKs在乳腺癌中的表达模式及预后意义:一项综合生物信息学研究。
背景:在全球范围内,乳腺癌(BC)已成为最常见的恶性肿瘤之一,也是女性肿瘤相关死亡的主要原因。细胞周期失调是癌症发展和转移的一个众所周知的标志。CDKs是细胞周期调控系统的重要组成部分,在包括BC在内的多种癌症中表达异常。在靶向癌症治疗的发展中,通过调节CDKs来重建细胞周期的调节已经成为一种很有前途的方法。方法采用生物信息学方法评估CDKs在BC中的表达模式、预后和诊断重要性以及临床相关性。此外,我们使用STRING和KEGG数据库对不受调控的CDKs进行了功能富集分析,以描述CDKs在乳腺肿瘤发生中的作用。结果基因表达分析显示BC中CDKs的显著失调,CDK1、CDK11A和CDK18的变化为>±1.5倍。此外,在原发性和转移性乳腺肿瘤的单细胞RNA测序分析中,转移性肿瘤显示CDK1高表达。此外,研究发现CDK表达失调影响BC患者的总生存期(OS)和无复发生存期(RFS)。结论该研究的多模态分析方法表明,调节CDKs治疗BC是一种很有前途的方法。
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来源期刊
Cancer Biomarkers
Cancer Biomarkers ONCOLOGY-
CiteScore
5.20
自引率
3.20%
发文量
195
审稿时长
3 months
期刊介绍: Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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