Instituto de Investigación Biomédica de Málaga - IBIMA; Medical Oncology Service, Section of Immuno-Oncology, Hospitales Universitarios Regional y Virgen de la Victoria; C/ Marqués de Beccaría n°3, 29010, Málaga, Spain.
Instituto de Investigación Biomédica de Málaga - IBIMA; Research Unit. Hospital Costa del Sol. Research Network on Health Services in Chronic Diseases (REDISSEC). Autovía A-7, km 187, 29603 Marbella, Málaga, Spain; Surgery, Biochemistry and Immunology Department. Medical School, University of Málaga; 29010 Málaga, Spain.
Semin Cancer Biol. 2022 Aug;83:584-595. doi: 10.1016/j.semcancer.2021.03.012. Epub 2021 Mar 20.
Cancer is the second leading cause of death worldwide being responsible for 9.6 million deaths in 2018. Epigenetic alterations are key in directing the aberrant expression of tumor-associated genes that drive cellular malignant transformation and cancer progression. Among epigenetic alterations, DNA methylation is the most deeply studied one in relation to environmental exposure. Tissue biopsies have traditionally been the main procedure by which a small sample of body tissue is excised to confirm cancer diagnosis or to indicate the primary site when cancer has spread. In contrast, the analysis of circulating tumor-derived material, or tumor circulome, by means of liquid biopsy of peripheral blood, urine, saliva or sputum is a noninvasive, fast and reproducible alternative to tissue biopsy. Recently, the assessment of epigenetic alterations such as DNA methylation and hydroxymethylation in circulating free DNA has been proved possible. These marks can be associated to prognosis and response to a variety of treatments including chemotherapy, hormonotherapy or immunotherapy. Epigenetic biomarkers may offer some advantages over RNA or genetic biomarkers given their stability in bodily fluids and their high tissue-specificity. While many challenges are still ahead, the unique advantages of these types of biomarkers is urging the scientific community to persevere in their clinical validation and integration into reliable prediction models. This review aims at recapitulating the emerging noninvasive DNA methylated biomarkers of importance for prediction of prognosis and drug response in cancer.
癌症是全球第二大死亡原因，2018 年导致 960 万人死亡。表观遗传改变是指导肿瘤相关基因异常表达的关键，这些基因驱动着细胞恶性转化和癌症进展。在表观遗传改变中，DNA 甲基化是与环境暴露关系最密切的研究之一。组织活检一直是传统的主要程序，通过该程序切除身体组织的一小部分样本，以确认癌症诊断或在癌症扩散时指示原发部位。相比之下，通过外周血、尿液、唾液或痰液的液体活检对循环肿瘤衍生物质或肿瘤循环组的分析是一种非侵入性、快速且可重复的组织活检替代方法。最近，已经证明可以评估循环游离 DNA 中的表观遗传改变，如 DNA 甲基化和羟甲基化。这些标记物可以与预后以及对各种治疗方法（包括化疗、激素治疗或免疫治疗）的反应相关联。与 RNA 或遗传生物标志物相比，表观遗传生物标志物具有一些优势，因为它们在体液中的稳定性和组织特异性高。尽管仍面临许多挑战，但这些类型生物标志物的独特优势促使科学界坚持不懈地对其进行临床验证并整合到可靠的预测模型中。本综述旨在回顾用于预测癌症预后和药物反应的新兴非侵入性 DNA 甲基化生物标志物。
