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放疗改变头颈部癌症患者的唾液蛋白质组:治疗前后的评估。

Radiotherapy changes the salivary proteome in head and neck cancer patients: evaluation before, during, and after treatment.

机构信息

Department of Biological Sciences - Discipline of Biochemistry, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-90, Brazil.

Department of Surgery, Stomatology, Pathology and Radiology - Discipline of Radiology and Stomatology, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-90, Brazil.

出版信息

Clin Oral Investig. 2022 Jan;26(1):225-258. doi: 10.1007/s00784-021-03995-5. Epub 2021 May 29.

Abstract

OBJECTIVES

Salivary glands are affected during radiotherapy in the head and neck region, leading to a reduction in salivary flow and changes its composition. Besides negatively affecting the oral soft tissues, this can also lead to dental impairment. Thus, we evaluated the effect of radiotherapy in the proteomic profile of the saliva in patients with head and neck cancer (HNC).

MATERIALS AND METHODS

HNC patients had their saliva collected before (BRT), during (2-5 weeks; DRT), and after (3-4 months; ART) radiotherapy. Saliva was also collected from healthy volunteers (control; C). Samples were processed for proteomic analysis.

RESULTS

In total, 1055 proteins were identified, among which 46 were common to all groups, while 86, 86, 286, and 395 were exclusively found in C, BRT, DRT, and ART, respectively. Remarkably, alpha-enolase was increased 35-fold DRT compared with BRT, while proline-rich proteins were decreased. ART there was a 16-fold increase in scaffold attachment factor-B1 and a 3-fold decrease in alpha-enolase and several cystatins. When compared with C, salivary proteins of BRT patients showed increases cystatin-C, lysozyme C, histatin-1, and proline-rich proteins CONCLUSION/CLINICAL REVELANCE: Both HNC and radiotherapy remarkably change the salivary protein composition. Altogether, our results, for the first time, suggest investigating alpha-enolase levels in saliva DRT in future studies as a possible biomarker and strategy to predict the efficiency of the treatment. Moreover, our data provide important insights for designing dental products that are more effective for these patients and contribute to a better understanding of the progressive changes in salivary proteins induced by radiotherapy. Graphical abstract.

摘要

目的

头颈部放疗会影响唾液腺,导致唾液流量减少和成分改变。除了对口腔软组织产生负面影响外,还可能导致牙齿损伤。因此,我们评估了头颈部癌症(HNC)患者放疗对唾液蛋白质组的影响。

材料与方法

HNC 患者在放疗前(BRT)、放疗中(2-5 周;DRT)和放疗后(3-4 个月;ART)收集唾液。还从健康志愿者(对照;C)中收集唾液样本。对样本进行蛋白质组分析。

结果

共鉴定出 1055 种蛋白质,其中 46 种存在于所有组中,而 86、86、286 和 395 种分别仅存在于 C、BRT、DRT 和 ART 中。值得注意的是,与 BRT 相比,DRT 中 alpha-烯醇酶增加了 35 倍,而富含脯氨酸的蛋白质减少。ART 中支架附着因子-B1 增加了 16 倍,alpha-烯醇酶和几种胱抑素减少了 3 倍。与 C 相比,BRT 患者的唾液蛋白中胱抑素-C、溶菌酶 C、组氨酸-1 和富含脯氨酸的蛋白质增加。

结论/临床意义:HNC 和放疗都会显著改变唾液蛋白组成。总之,我们的研究结果首次表明,在未来的研究中,可能需要检测 DRT 唾液中 alpha-烯醇酶水平,作为预测治疗效果的潜在生物标志物和策略。此外,我们的数据为设计更适合这些患者的口腔护理产品提供了重要的见解,并有助于更好地理解放疗引起的唾液蛋白渐进性变化。

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