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预测头颈癌患者治疗反应的生物标志物的蛋白质组学分析

Proteomic Analysis of Biomarkers Predicting Treatment Response in Patients with Head and Neck Cancers.

作者信息

Zebene Emeshaw Damtew, Lombardi Rita, Pucci Biagio, Medhin Hagos Tesfay, Seife Edom, Di Gennaro Elena, Budillon Alfredo, Woldemichael Gurja Belay

机构信息

Nuclear Medicine Unit, Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa 9086, Ethiopia.

Department of Microbial Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa 9086, Ethiopia.

出版信息

Int J Mol Sci. 2024 Nov 21;25(23):12513. doi: 10.3390/ijms252312513.

Abstract

Head and neck cancers (HNCs) are the sixth most commonly diagnosed cancer and the eighth leading cause of cancer-related mortality worldwide, with squamous cell carcinoma being the most prevalent type. The global incidence of HNCs is steadily increasing, projected to rise by approximately 30% per year by 2030, a trend observed in both developed and undeveloped countries. This study involved serum proteomic profiling to identify predictive clinical biomarkers in cancer patients undergoing chemoradiotherapy (CRT). Fifteen HNC patients at Tikur Anbessa Specialized Hospital, Radiotherapy (RT) center in Addis Ababa were enrolled. Serum samples were collected before and after RT, and patients were classified as responders (R) or non-responders (NR). Protein concentrations in the serum were determined using the Bradford assay, followed by nano-HPLC-MS/MS for protein profiling. Progenesis QI for proteomics identified 55 differentially expressed proteins (DEPs) between R and NR, with a significance of < 0.05 and a fold-change (FC) ≥ 1.5. The top five-up-regulated proteins included , , , , and , while the top five-down-regulated proteins were , , , , and . Notably, about 16.4% of the DEPs were involved in cellular responses to DNA damage from cancer treatments, encompassing proteins related to deoxyribonucleic acid (DNA) damage sensing, checkpoint activation, DNA repair, and apoptosis/cell cycle regulation. The analysis of the relative abundance of ten proteins with high confidence scores identified three DEPs: , , and as potential predictive biomarkers for treatment response. This study highlighted the identification of three potential predictive biomarkers-, , and -through serum proteomic profiling in HNC patients undergoing RT, emphasizing their significance in predicting treatment response.

摘要

头颈癌(HNCs)是全球第六大最常被诊断出的癌症,也是癌症相关死亡的第八大主要原因,其中鳞状细胞癌是最常见的类型。全球头颈癌的发病率正在稳步上升,预计到2030年每年将增长约30%,这一趋势在发达国家和不发达国家都有观察到。本研究涉及血清蛋白质组分析,以识别接受放化疗(CRT)的癌症患者的预测性临床生物标志物。招募了亚的斯亚贝巴提库尔·安贝萨专科医院放疗(RT)中心的15名头颈癌患者。在放疗前后收集血清样本,并将患者分为反应者(R)或无反应者(NR)。使用Bradford法测定血清中的蛋白质浓度,随后进行纳升液相色谱-串联质谱(nano-HPLC-MS/MS)分析蛋白质谱。蛋白质组学的Progenesis QI软件识别出反应者和无反应者之间有55种差异表达蛋白(DEPs),其显著性<0.05,倍数变化(FC)≥1.5。上调幅度最大的前五种蛋白质包括……,……,……,……和……,而下调幅度最大的前五种蛋白质是……,……,……,……和……。值得注意的是,约16.4%的差异表达蛋白参与了癌症治疗引起的细胞对DNA损伤的反应,包括与脱氧核糖核酸(DNA)损伤感知、检查点激活、DNA修复以及凋亡/细胞周期调控相关的蛋白质。对十种具有高置信度分数的蛋白质的相对丰度分析确定了三种差异表达蛋白:……,……和……作为治疗反应的潜在预测生物标志物。本研究强调了通过对头颈癌放疗患者的血清蛋白质组分析识别出三种潜在的预测生物标志物——……,……和……,强调了它们在预测治疗反应中的重要性。

(原文中部分蛋白名称未给出具体内容,所以用“……”代替)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/11641594/91aac06312da/ijms-25-12513-g001.jpg

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