综述

DNA甲基化检测助力肿瘤早期筛查和诊断

展开
  • 南通大学附属医院病理科,江苏 南通 226001

收稿日期: 2023-06-11

  网络出版日期: 2023-12-18

基金资助

国家自然科学基金面上项目(82273422);上海浦东新区科技发展基金资助(PKX2021-S09)

DNA methylation detection assists early screening and diagnosis of tumors

Expand
  • Department of Pathology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China

Received date: 2023-06-11

  Online published: 2023-12-18

摘要

DNA甲基化是国内外癌症早筛采用的常用检测指标。在致癌因素的作用下,抑癌基因启动子区的高甲基化可导致基因表达下调或关闭,从而激活原癌基因的表达,促使肿瘤发生。用于DNA甲基化检测的样本主要采用脱落细胞、血液样本和石蜡包埋组织。常用的检测方法包括特异性聚合酶链反应(methylation-specific polymerase chain reaction, MSP)、核酸质谱、甲基化芯片、亚硫酸氢盐测序、第二代测序技术等。与突变检测相比,DNA甲基化的检测优势在于其肿瘤特异性高、可检测位点多、信号丰度高,且可实现组织溯源。目前,DNA甲基化检测被主要运用在临床脑胶质瘤用药指导、肺癌辅助诊断和高危分流、膀胱癌高危分流和复发监测、宫颈癌高危分流、结直肠癌和胃癌早期筛查及复发监测。在实现大规模临床常规应用前,需注意精准定位DNA甲基化检测的应用场景,相对于耐受性良好的内镜检查,其高危分流的刚需性可能会下降。在辅助诊断病理诊断灵敏度较低的肿瘤、肿瘤监测和预后评估方面,DNA甲基化检测有着重要的作用。随着检测流程和质量管理的规范,DNA甲基化检测会被更广泛地运用于临床,提高肿瘤的早筛和诊断灵敏度。

本文引用格式

刘益飞 . DNA甲基化检测助力肿瘤早期筛查和诊断[J]. 诊断学理论与实践, 2023 , 22(04) : 393 -401 . DOI: 10.16150/j.1671-2870.2023.04.011

Abstract

DNA methylation is one of the most widely used indicator for early cancer screening. Under the influence of carcinogens, hypermethylation of the promoter region of tumor suppressor genes may lead to downregulation or silencing of gene expression, thereby activating the expression of proto-oncogenes and promoting tumorigenesis. The samples used for DNA methylation detection are mainly exfoliated cells, blood samples and paraffin-embedded tissues. Commonly used detection methods include: methylation-specific polymerase chain reaction (MSP), nucleic acid mass spectrometry, methylation chip, bisulfite sequencing, next-generation sequencing, etc. Compared with mutation detection, the advantages of DNA methylation detection are that it has higher tumor specificity, more detectable sites, higher signal quality, and can achieve tissue traceability. Currently, it is mainly used clinically for medication guidance for brain glioma, aid in diagnosis and high-risk triage for lung cancer, high-risk triage and recurrence monitoring for bladder cancer, high-risk triage for cervical cancer, and early screening and recurrence monitoring for colorectal cancer and gastric cancer. Before large-scale clinical routine application, accurately positioning of the application scenarios for DNA methylation detection must be considered. For well-tolerated endoscopy, the rigid need of DNA methylation detection for high-risk triage may be reduced. DNA methylation detection plays an important role in assisting in the diagnosis of tumors with low pathological diagnosis sensitivity, tumor monitoring and prognosis assessment. With the standardization of testing procedures and quality management, DNA methylation detection will be more widely used to improve the early screening and diagnostic sensitivity of tumors.

参考文献

[1] SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[2] LI S, TOLLEFSBOL T O. DNA methylation methods: Global DNA methylation and methylomic analyses[J]. Methods, 2021, 187:28-43.
[3] LIU MC, OXNARD GR, KLEIN EA, et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA[J]. Ann Oncol, 2020, 31(6):745-759.
[4] YIZHAK K, AGUET F, KIM J, et al. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues[J]. Science, 2019, 364(6444):eaaw0726.
[5] 杨林林, 蒋涛, 隋亚鑫, 等. DNA甲基化检测技术[J]. 标记免疫分析与临床, 2020, 27(5):898-904.
[5] YANG L L, JIANG T, SUI Y X, et al. DNA Methylation Detection Technology[J]. Lab Immunoassay & Clin Med, 2020, 27(5):898-904.
[6] 杨晋生, 古选民, 方军超. 胶质瘤MGMT启动子甲基化及其临床意义[J]. 临床肿瘤学杂志, 2019, 24(2):153-157.
[6] YANG J S, GU X M, FANG J C. Methylation of MGMT promoter in glioma and its clinical significance[J]. Chin Clin Oncol, 2019, 24(2):153-157.
[7] 樊星, 刘幸, 柴睿超, 等. 2020版美国国立综合癌症网络脑胶质瘤临床实践指南解读[J]. 中华神经外科杂志, 2021, 37(6): 541-545.
[7] FAN X, LIU X, CHAI R C, et al. Interpretation of the 2020 National Comprehensive Cancer Network Clinical Practice Guidelines for Gliomas in the United States[J]. Chin J Neurosurg, 2021, 37(6): 541-545.
[8] ZHANG C, YU W, WANG L, et al. DNA methylation analysis of the SHOX2 and RASSF1A panel in bronchoalveolar lavage fluid for lung cancer diagnosis[J]. J Cancer, 2017, 8(17):3585-3591.
[9] 陈瑞英, 刘雅, 孙婷, 等. 支气管肺泡灌洗液中SHOX2和RASSF1A基因甲基化检测对肺癌的诊断价值[J]. 郑州大学学报(医学版), 2019, 54(5):732-736.
[9] CHEN R Y, LIU Y, SUN T, et al. Value of DNA methylation analysis of SHOX2 and RASSF1A in bron-choalveolar lavage fluid in diagnosis of lung cancer[J]. J Zhengzhou Univ( Med Sci), 2019, 54(5):732-736.
[10] 张彤, 王晓伟, 吴俊秀, 等. SHOX2RASSF1A基因甲基化在非小细胞肺癌小活检样本临床病理诊断中的应用价值[J]. 诊断病理学杂志, 2022, 29(5):389-394.
[10] ZHANG T, WANG X W, WU J X, et al. Application value of SHOX2 and RASSF1A gene methylation in clinicopathological diagnosis of small biopsy samples of non-small cell lung cancer[J]. J Diag Pathol, 2022, 29(5):389-394.
[11] SHI J, CHEN X, ZHANG L, et al. Performance evaluation of SHOX2 and RASSF1A methylation for the aid in diagnosis of lung cancer based on the analysis of FFPE specimen[J]. Front Oncol, 2020, 10:565780.
[12] ZHANG N, LIU Z, LI K, et al. DNA methylation analysis of the SHOX2 and RASSF1A panel using cell-free DNA in the diagnosis of malignant pleural effusion[J]. J Oncol, 2023, 2023:5888844.
[13] LIANG C, LIU N, ZHANG Q, et al. A detection panel of novel methylated DNA markers for malignant pleural effusion[J]. Front Oncol, 2022, 12:967079.
[14] XING W, SUN H, YAN C, et al. A prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant from benign pulmonary nodules[J]. BMC Cancer, 2021, 21(1):263.
[15] TAN W S, FEBER A, SARPONG R, et al. Who should be investigated for haematuria? Results of a contemporary prospective observational study of 3556 patients[J]. Eur Urol, 2018, 74(1):10-14.
[16] 张晗, 林琳, 杞朝梅, 等. DNA甲基化在宫颈病变和宫颈癌中的临床研究进展[J]. 中国妇幼保健, 2021, 36(20):4873-4875.
[16] ZHANG H, LIN L, QI C M, et al. Clinical research progress of DNA methylation in cervical lesions and cervical cancer[J]. Matern Child Health Care China, 2021, 36(20):4873-4875.
[17] SCHMITZ M, EICHELKRAUT K, SCHMIDT D, et al. Performance of a DNA methylation marker panel using liquid-based cervical scrapes to detect cervical cancer and its precancerous stages[J]. BMC Cancer, 2018, 18(1):1197.
[18] SHI L, YANG X, HE L, et al. Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens[J]. BMC Cancer, 2023, 23(1):168.
[19] LI B, GUO R, LAI T, et al. The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening[J]. J Obstet Gynaecol Res, 2021, 47(8):2720-2728.
[20] SONG L, YU H, JIA J, et al. A systematic review of the performance of the SEPT9 gene methylation assay in colorectal cancer screening, monitoring, diagnosis and prognosis[J]. Cancer Biomark, 2017, 18(4):425-432.
[21] XU F, YU S, HAN J, et al. Detection of circulating tumor DNA methylation in diagnosis of colorectal cancer[J]. Clin Transl Gastroenterol, 2021, 12(8):e00386.
[22] BURKE C A, LIEBERMAN D, FEUERSTEIN J D. AGA clinical practice update on approach to the use of noninvasive colorectal cancer screening options: commentary[J]. Gastroenterology, 2022, 162(3):952-956.
[23] XIE L, JIANG X, LI Q, et al. Diagnostic value of methy-lated Septin9 for colorectal cancer detection[J]. Front Oncol, 2018, 8:247.
[24] LI S, CHEN M, LI Y, et al. Prenatal epigenetics diets play protective roles against environmental pollution[J]. Clin Epigenetics, 2019, 11(1):82.
[25] LU P, ZHU X, SONG Y, et al. Methylated Septin 9 as a promising biomarker in the diagnosis and recurrence monitoring of colorectal cancer[J]. Dis Markers, 2022, 2022:7087885.
[26] LIU W, HU P, LIU J, et al. mSEPT9 can monitor the response and predict the prognosis of stage Ⅳ colorectal cancer patients with liver metastasis undergoing potentially curative surgery[J]. J Surg Res, 2021, 267:485-494.
[27] XU H, CHEN H, HU J, et al. Feasibility of quantification based on novel evaluation with stool DNA and fecal immunochemical test for colorectal cancer detection[J]. BMC Gastroenterol, 2022, 22(1):384.
[28] 陈旻, 黄一鸣, 赵晖, 等. 胰腺癌血浆循环游离DNA甲基化预测模型的构建及应用[J]. 肿瘤, 2021, 41(08): 541-549.
[28] CHEN Min, HUANG Yiming, ZHAO Hui, et al. Construction and application of plasma cell-free DNA methylation prediction model for pancreatic cancer[J]. Tumor, 2021, 41(08): 541-549.
[29] 刘玉玲, 梁顺顺, 徐慧莉, 等. miR-103/MTHFR轴抑制肝细胞癌中LINE-1基因的甲基化水平[J]. 肿瘤, 2022, 42(02): 93-107.
[29] LIU Yuling, LIANG Shunshun, XU Huili, et al. MiR-103/MTHFR axis inhibits the DNA methylation of LINE-1 gene in hepatocellular carcinoma[J]. Tumor, 2022, 42(2): 93-107.
[30] 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1):19-28.
[30] ZHENG R S, SUNK X, ZHANG S W, et al. Report of cancer epidemiology in China, 2015[J]. Chin J Oncol, 2019, 41(1):19-28.
文章导航

/