Serological proteomic profiling uncovered CDK5RAP2 as a novel marker in benign prostatic hyperplasia

IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Clinical biochemistry Pub Date : 2025-01-01 DOI:10.1016/j.clinbiochem.2024.110867
Huan Xie , Junli Fan , Jiajun Wang , Tao Liu , Lili Chen , Yunbao Pan , Yirong Li , Xinran Li
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Abstract

Background

Benign prostatic hyperplasia (BPH) affects approximately half of men over the age of 50. Early detection and timely treatment facilitate disease intervention and achieve a better clinical outcome. However, current clinical methods, such as prostate specific antigen (PSA), lack the sensitivity to accurately distinguish between BPH and prostate cancer (PCa). Thus, optimal serum markers are warranted to complement existing diagnostic tests.

Methods

In this study, we recruited 1987 BPH patients and characterized their clinical features. To explore BPH proteomic alterations, a data independent acquisition-based mass spectrometry proteomics approach was adopted for 66 serum samples from healthy males (n = 22), patients with BPH (n = 22) and prostate cancer (n = 22). Bioinformatic evaluations were performed for proteomic profiling and candidate selection. In addition, a promising candidate was further validated with ELISA assay.

Results

Our findings revealed that the level of free PSA correlated with prostate volume. 7.95 % of BPH patients had a PSA value greater than 10 ng/mL, with elevated free PSA, prostate volume, PSA density, and decreased free to total PSA ratio. Mass spectrometry-based serum profiling demonstrated distinct differences between BPH and PCa. CDK5RAP2 was weighted most important in BPH patients’ serum and achieved an area under the receiver operating characteristic curve of 0.900 in distinguishing BPH and PCa, which was further validated by publicly-available mRNA microarray analysis and cellular phenotype evaluation.

Conclusion

Our comprehensive analysis systematically explored BPH serum characteristics, proteomic profiles, and identified novel serum markers that may contribute to the understanding of BPH and facilitate early diagnosis and intervention.
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血清学蛋白质组学分析发现CDK5RAP2是良性前列腺增生的新标志物。
背景:50岁以上的男性中约有一半患有良性前列腺增生(BPH)。早期发现和及时治疗有利于疾病干预,达到较好的临床效果。然而,目前的临床方法,如前列腺特异性抗原(PSA),缺乏准确区分BPH和前列腺癌(PCa)的敏感性。因此,最佳的血清标记物是必要的,以补充现有的诊断测试。方法:在本研究中,我们招募了1987例BPH患者,并对其临床特征进行了分析。为了探讨前列腺增生蛋白组学的改变,采用数据独立获取的质谱蛋白质组学方法,对健康男性(n = 22)、前列腺增生患者(n = 22)和前列腺癌患者(n = 22)的66份血清样本进行了研究。进行生物信息学评估以进行蛋白质组学分析和候选物选择。另外,利用ELISA进一步验证了一种有希望的候选药物。结果:游离PSA水平与前列腺体积相关。7.95 % BPH患者PSA值大于10 ng/mL,游离PSA、前列腺体积、PSA密度升高,游离PSA与总PSA之比降低。基于质谱的血清谱分析显示BPH和PCa之间存在明显差异。CDK5RAP2在BPH患者血清中权重最大,在区分BPH和PCa时,其受体算子曲线下面积为0.900,通过mRNA微阵列分析和细胞表型评价进一步验证了这一点。结论:我们的综合分析系统地探讨了BPH的血清特征、蛋白质组学特征,并发现了新的血清标记物,这些标记物可能有助于了解BPH并促进早期诊断和干预。
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来源期刊
Clinical biochemistry
Clinical biochemistry 医学-医学实验技术
CiteScore
5.10
自引率
0.00%
发文量
151
审稿时长
25 days
期刊介绍: Clinical Biochemistry publishes articles relating to clinical chemistry, molecular biology and genetics, therapeutic drug monitoring and toxicology, laboratory immunology and laboratory medicine in general, with the focus on analytical and clinical investigation of laboratory tests in humans used for diagnosis, prognosis, treatment and therapy, and monitoring of disease.
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