放化疗性口腔黏膜炎相关生物标志物研究进展  

Research progress on biomarkers related to radiotherapy and/or chemotherapy⁃induced oral mucositis

作　　者：凌云霄 王建涛[2] 王艳[1] LING Yunxiao;WANG Jiantao;WANG Yan(State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases,Department of Pediatric Dentistry,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China;State Key Laboratory of Biotherapy&Department of Lung Cancer Center and Department of Radiation Oncology,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]口腔疾病研究国家重点实验室,国家口腔疾病临床医学研究中心,四川大学华西口腔医院儿童口腔科,四川成都610041 [2]生物治疗国家重点实验室,四川大学华西医院肺癌中心,四川大学华西医院放疗中心,四川成都610041

出　　处：《口腔疾病防治》2021年第4期260-266,共7页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金项目(81600864);四川省卫计委基金普及项目(18PJ186)。

摘　　要：放化疗性口腔黏膜炎是肿瘤患者进行放疗和(或)化疗时常见的口腔局部并发症,严重降低患者的生活质量,甚至影响抗肿瘤治疗。生物标志物是在疾病发生前或过程中在不同生物学水平上出现的信号指标。全面了解口腔黏膜炎相关生物标志物有助于早期识别口腔黏膜炎高风险患者及筛选易发展成为严重口腔黏膜炎的患者,从而指导针对口腔黏膜炎的防治。本文对现有口腔黏膜炎相关生物标志物予以综述。文献复习结果表明,口腔黏膜炎相关生物标志物包括生长因子、炎性细胞因子、基因、血浆抗氧化剂以及促凋亡/抗凋亡蛋白等。这些生物标志物可用来预测口腔黏膜炎的风险或者早期识别易发生严重放化疗性口腔黏膜炎的患者,其中上皮生长因子、肿瘤坏死因子α、白细胞介素⁃6、白细胞介素⁃1β及C反应蛋白可用来预测和评估口腔黏膜炎发生风险及发展程度;剪切修复交叉互补基因1(excision repair cross complementing 1,ER⁃CC1)、X射线交错互补修复基因1(X⁃ray repair cross complementing 1,XRCC1)、甲酰四氢叶酸还原酶(methy⁃lenetetrahydrofolate reductase,MTHFR)及肿瘤坏死因子受体超家族成员1A(tumor necrosis factor receptor super⁃family member 1A,TNFRSF1A)等基因是近年研究热点,部分基因型及表达量对口腔黏膜炎的风险及严重程度有不同程度的预测能力。但目前尚未有生物标志物用于临床,未来需要更多的研究对这些生物标志物的可靠性及准确性进行验证,为放化疗口腔黏膜炎的早期精准防治提供参考。Radiotherapy and/or chemotherapy⁃induced oral mucositis is a common oral complication in tumor pa⁃tients undergoing radiotherapy and/or chemotherapy,which seriously compromises patients’quality of life and even af⁃fects anti⁃tumor treatment.Biomarkers are signal indicators that appear at different biological levels before or during dis⁃ease.A comprehensive understanding of the biomarkers associated with oral mucositis contributes to the early identifica⁃tion of high⁃risk patients with oral mucositis and aids in the screening of patients prone to develop severe oral mucositis,guiding the prevention and treatment of oral mucositis.This article reviews the existing biomarkers associated with oral mucositis.The literature review results showed that the biomarkers associated with oral mucositis included growth fac⁃tors,inflammatory cytokines,genes,plasma antioxidants,and pro⁃apoptotic proteins/inhibitor of apoptosis proteins.These biomarkers can be used to predict the risk of oral mucositis or facilitate early discrimination of patients prone to exhibit severe radiotherapy and/or chemotherapy⁃induced oral mucositis.EGF,TNF⁃α,IL⁃6,IL⁃1βand CRP can be used to predict and evaluate the risk and development of oral mucositis,whereas genes such as excision repair cross complementing 1(ERCC1),X⁃ray repair cross complementing 1(XRCC1),methylenetetrahydrofolate reductase(MTHFR)and tumor necrosis factor receptor superfamily member 1A(TNFRSF1A)have been focus of research in recent years.The genotypes and expression levels of some of these genes exhibit variable capacities to predict the risk and severity of oral mucositis.However,no biomarkers have been used in clinical practice,and more studies are needed in the future to verify the reliability and accuracy of these biomarkers,to provide a reference for the early accurate prevention and treatment of radiation and chemotherapy oral mucositis.

关 键 词：口腔黏膜炎 放化疗性口腔黏膜炎 放疗 化疗 生物标志物 上皮生长因子 血管内皮生长因子 碱性成纤维细胞生长因子 肿瘤坏死因子⁃α 白细胞介素 剪切修复交叉互补基因l X射线交错互补修复基因1 甲酰四氢叶酸还原酶 

分 类 号：R86[医药卫生—临床医学]