国际口腔医学杂志

国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (1): 68-75.doi: 10.7518/gjkq.2020017

• 综述 • 上一篇    下一篇

唾液生物标志物在口腔癌筛查中的应用

黄璐1,2,戴杰3,吴燕岷1,()   

  1. 1. 浙江大学医学院附属第二医院口腔内科 杭州 310009
    2. 杭州市大江东医院口腔科 杭州 311225
    3. 台州医院路桥院区口腔科 台州 318050
  • 收稿日期:2019-03-19 修回日期:2019-09-28 出版日期:2020-01-01 发布日期:2020-01-01
  • 通讯作者: 吴燕岷 E-mail:wuyanmin@zju.edu.cn
  • 作者简介:黄璐,主治医师,学士,Email： huanglupl@163.com
  • 基金资助:
    浙江省科技厅公益研究计划(LGF18H140003)

Application of saliva biomarkers in oral cancer screening

Huang Lu1,2,Dai Jie3,Wu Yanmin1,()   

  1. 1. Dept. of Oral Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
    2. Dept. of Stomatology, The Dajiangdong Hospital, Hangzhou 311225, China
    3. Dept. of Stomatology, Luqiao Hospital District, Taizhou Hospital, Taizhou 318050, China
  • Received:2019-03-19 Revised:2019-09-28 Online:2020-01-01 Published:2020-01-01
  • Contact: Yanmin Wu E-mail:wuyanmin@zju.edu.cn
  • Supported by:
    This study was supported by Science and Technology Department Public Welfare Research Plan of Zhejiang Province(LGF18H140003)

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摘要：

唾液含有丰富的DNA、RNA、蛋白质、微生物及代谢产物。它作为一种无创、安全的来源,可以替代血液用于疾病的诊断和预后。随着微阵列技术、全基因组测序、全转录组测序等高通量技术的快速发展,研究发现唾液是一个潜在的巨大生物标志物储存库,已有多种疾病特异性唾液标志物被挖掘。本文整合了已报道的有关口腔癌及癌前筛查的唾液生物标志物,探讨了唾液作为该领域生物标志物的优缺点及改进策略,以期为将来口腔癌的早期诊断及治疗提供参考。

关键词: 唾液, 口腔癌, 癌前筛查, 生物标志物, 精准医疗

Abstract:

Saliva secreted by salivary glands is rich in DNA, RNA, proteins, microorganisms and metabolites. As a noninvasive and safe source, saliva can replace blood in the diagnosis and prognosis of diseases. With the rapid development of microarray technology, whole-genome sequencing, whole-transcriptome sequencing and other high-throughput technologies, this study found that saliva is a potential huge biomarker repository and excavated many disease-specific saliva markers. The saliva biomarkers were integrated for oral cancer and precancer screening. The advantages and disadvantages of using saliva as a biomarker in this field and as an improvement strategy were discussed to provide insights into the early diagnosis and treatment of oral cancer in the future.

Key words: saliva, oral cancer, pre-cancer screening, biomarker, precision medicine

中图分类号: 

  • R730.4

表 1

口腔癌及癌前筛查的潜在唾液生物标志物汇总"

唾液生物标志物 类别 检测方法 结果 文献
IL-8、IL-1β 蛋白质 ELISA、Luminex xMAP 口腔鳞状细胞癌患者中IL-8和IL-1β表达水平显著偏高 [12]
液相芯片技术
乙醛脱氢酶 蛋白质 荧光分析 口腔鳞状细胞癌患者中乙醛脱氢酶活性偏高 [17]
癌胚抗原、癌抗原-50 蛋白质 ELISA、放射免疫法 恶性肿瘤患者中癌胚抗原和癌抗原-50水平显著偏高 [18]
四连接素 蛋白质 二维凝胶电泳 四连接素在口腔鳞状细胞癌转移患者中低表达 [19]
半胱氨酸蛋白酶抑制物SA-1 蛋白质 激光脱附/电离飞行时间 口腔鳞状细胞癌患者中半胱氨酸蛋白酶抑制剂SA-1被截短 [20]
质谱
转铁蛋白 蛋白质 二维电泳、ELISA、We- 口腔癌患者中转铁蛋白水平偏高 [21]
stern blot、基质辅助激光
解析电离飞行时间质谱
IL-8 蛋白质 ELISA 口腔癌患者的IL-8水平较高 [22-24]
抗原125 蛋白质 ELISA 口腔癌患者癌症抗原125水平偏高 [25]
基质金属蛋白酶 蛋白质 qRT-PCR及矩阵分析 口腔鳞状细胞癌患者的基质金属蛋白酶-1、基质金属蛋白酶- [26]
3显著偏高
IL-6、肿瘤坏死因子-α 蛋白质 ELISA 口腔癌患者唾液中肿瘤坏死因子-α和IL-6水平显著高于正常 [27]
对照组和癌前患者
膜联蛋白1、过氧化物酶2 蛋白质 电泳 膜联蛋白1和过氧化物酶2仅在口腔癌患者中表达 [28]
角蛋白10 蛋白质 二维电泳 口腔白斑患者角蛋白10免疫阳性 [29]
趋化素、基质金属蛋白酶9 蛋白质 ELISA 口腔鳞状细胞癌患者趋化素、基质金属蛋白酶9水平明显高于 [30]
口腔癌前病变患者
表皮生长因子受体 蛋白质 ELISA 口腔鳞状细胞癌患者表皮生长因子受体表达水平低 [31]
基质金属蛋白酶9 蛋白质 ELISA 口腔鳞状细胞癌患者基质金属蛋白酶9水平显著升高 [32]
内皮素-1 蛋白质 ELISA 口腔鳞状细胞癌患者、口腔扁平苔藓患者内皮素-1水平偏高 [33]
核转运蛋白A2、基质金属蛋 蛋白质 qRT-PCR、ELISA 口腔鳞状细胞癌患者核转运蛋白A2表达量高,基质金属蛋 [34]
白酶、IL-1β、核因子-κB 白酶、IL-1β、核因子-κB水平偏高
唾液生物标志物 类别 检测方法 结果 文献
腺苷脱氨酶 DNA ELISA 舌癌患者中腺苷脱氨酶水平偏高 [35]
E-钙黏附蛋白、TMEFF2*、 DNA 甲基化特异性PCR、微 口腔癌检查中E-钙黏附蛋白、TMEFF2和MGMT敏感性较高 [36]
MGMT# 芯片、电泳 且特异性强。E-钙黏附蛋白、TMEFF2、MGMT和维甲酸受
体β联合筛查口腔鳞状细胞癌时敏感性高、特异性强
人精脒/精胺乙酰转移酶、锌 mRNA 定量PCR芯片分析 口腔癌患者中IL-8、IL-1β、人精脒/精胺乙酰转移酶、锌指蛋 [37-38]
指蛋白1、H3组蛋白家族蛋白 白1、H3组蛋白家族蛋白3A和双特异性蛋白1水平显著偏高
3A、双特异性蛋白1、S100钙
结合蛋白P、IL
miR-200a、miR-125a 微小RNA qRT-PCR 口腔鳞状细胞癌患者miR-200a和miR-125a的表达显著偏低 [39]
miR-31 微小RNA qRT-PCR 口腔癌患者中miR-31的差异倍数中值显著偏高 [40]
miR-302b-3p、miR-517b-3p、 微小RNA qRT-PCR miR-302b-3p和miR-517b-3p仅在口腔鳞状细胞癌患者的细胞 [41]
miR-512-3p、miR-412-3p 外囊泡中表达;口腔鳞状细胞癌患者的唾液细胞外囊泡中
miR-512-3p和miR-412-3p表达上调
hsa_circ_0001874、 hsa_ circ_ 环状RNA qRT-PCR、微阵列分析 口腔鳞状细胞癌术后hsa_circ_0001874、hsa_circ_0001971水 [42]
0001971 平明显低于术前;hsa_circ_0001874与TNM分期、肿瘤分级
相关,hsa_circ_0001971与TNM分期相关
脂质过氧化物酶、羟基自由 氧化应激 组织芯片分析、ELISA 口腔鳞状细胞癌中羟基和过氧化氢自由基水平升高 [43]
基、超氧化物歧化酶 相关分子
糖皮质激素 皮质醇 ELISA 与吸烟者、饮酒者和黏膜白斑患者相比,口咽鳞状细胞癌患 [44]
者唾液中皮质醇水平更高
烟酰胺 维生素 代谢组学、Western blot 口腔鳞状细胞癌患者烟酰胺N-甲基转移酶水平上调 [45]
维生素C 维生素 2,4-二硝基苯肼法 潜在恶性疾病和口腔癌患者的平均维生素C水平显著降低 [46]
流感嗜血菌、棒杆菌、卟啉单 微生物 微生物生态学定量分析 口腔微生物组能够预测口腔癌和口咽癌的存在,敏感性和特 [47]
胞菌、罗卡利马氏体、芽孢杆菌 异性高
端粒酶 酶 PCR-ELISA 在口腔癌患者中表达 [48]
凋亡细胞 其他 TUNEL分析 口腔鳞状细胞癌中凋亡细胞显著减少 [49]
多标志物联合检测
肌动蛋白、肌球蛋白 蛋白质 质谱分析 确定口腔病变及其病前状态,肌动蛋白的敏感性和特异性分 [50]
别为100%和75%,肌动蛋白为67%和83%
总蛋白质、角蛋白19的片段 蛋白质 ELISA 口腔鳞状细胞癌组和癌前病变组CYFRA-21-1、乳酸脱氢酶和 [51]
CYFRA-21-1、乳酸脱氢酶、 总蛋白质水平均升高,但癌前病变组的升高明显低于口腔鳞
淀粉酶 状细胞癌组。口腔鳞状细胞癌组和癌前病变组中淀粉酶水平
明显降低
CD44v、SYNE1、miR34a 蛋白质、 甲基化特异性PCR、生 在口腔鳞状细胞癌患者中,CD44v6和CD44v10表达显著增 [52]
微小RNA 物信息学方法 加,而SYNE1和miR34a表达显著降低
过氧化酶-2、锌-2-糖蛋白 蛋白质 二维电泳、质谱分析、 口腔鳞状细胞癌患者过氧化酶-2和锌-2-糖蛋白水平显著上调 [53]
Western blot
唾液生物标志物 类别 检测方法 结果 文献
双特异性蛋白1、生长停滞和 mRNA 基因芯片 口腔鳞状细胞癌患者中双特异性蛋白1、生长停滞和DNA损 [22,54]
DNA损伤诱导因子β、H3组蛋 伤诱导因子β、H3组蛋白家族蛋白3A、IL-1β、IL-8、锌指蛋
白家族蛋白3A、IL-1β、IL-8、 白1、G蛋白信号转导的调节因子2、S100钙结合蛋白P、精脒/
锌指蛋白1、G蛋白信号转导 精胺乙酰转移酶的表达水平显著增高;IL-8、精脒/精胺乙酰
的调节因子2、S100钙结合蛋 转移酶、H3组蛋白家族蛋白3A联合检测口腔鳞状细胞癌,敏
白P、精脒/精胺乙酰转移酶 感性高
IL-1β、IL-8、锌指蛋白、精脒/ mRNA qRT-PCR IL-1β、IL-8、锌指蛋白和精脒/精胺乙酰转移酶的mRNA作为 [55]
精胺乙酰转移酶 标志物检测口腔鳞状细胞癌,准确率高达80%
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