Mohd Kamal Khairunnisa, Ghazali Ahmad Rohi, Ab Mutalib Nurul Syakima, Abu Nadiah, Chua Eng Wee, Masre Siti Fathiah
Biomedical Science Programme, Centre for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), 50300, Kuala Lumpur, Malaysia.
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia (UKM), 56000, Cheras, Kuala Lumpur, Malaysia.
Heliyon. 2024 Sep 27;10(19):e38663. doi: 10.1016/j.heliyon.2024.e38663. eCollection 2024 Oct 15.
Lung cancer as the second most death cancer reported cases is becoming a major threat to the global healthcare system. With the different subtypes of lung cancer and their limited therapy options due to the lack of targetable genes, rising cases of treatment resistance further complicate the management. The majority of the reported lung cancer cases are categorised as non-small cell lung cancer (NSCLC) which is highly associated with tobacco smoking. Tumorigenesis and cancer progression have also been associated with epigenetics. Epigenetics is responsible for cancer gene regulation and its reversible mechanisms attract the current trend of cancer management research. One of the most studied mechanisms is DNA methylation which can influence the cancer gene transcription outcomes. The enzyme, DNA methyltransferases (DNMTs) play a role in regulating the whole process of DNA methylation. Thus, abnormalities in DNMTs can lead to aberrant methylation patterns which then disturb the gene regulation and cellular functions as a whole. In this review, NSCLC subtypes are discussed with the current research trend of studies involving DNA methylation mechanism as a potential diagnostic and prognostic cancer biomarker. As DNMTs expression influences the methylation pattern, our review also outlined the abnormal pattern of DNMTs and its potential therapeutic target for NSCLC to restore the aberrant gene regulation and produce a better prognosis.
肺癌作为报告病例中第二大致死癌症，正成为全球医疗系统的重大威胁。由于肺癌存在不同亚型，且因缺乏可靶向基因导致治疗选择有限，治疗耐药病例的增加进一步使治疗管理复杂化。报告的肺癌病例大多被归类为非小细胞肺癌（NSCLC），它与吸烟高度相关。肿瘤发生和癌症进展也与表观遗传学有关。表观遗传学负责癌症基因调控，其可逆机制吸引了当前癌症管理研究的趋势。研究最多的机制之一是DNA甲基化，它可影响癌症基因转录结果。DNA甲基转移酶（DNMTs）在调节DNA甲基化的整个过程中发挥作用。因此，DNMTs异常可导致异常甲基化模式，进而扰乱基因调控和整体细胞功能。在本综述中，我们讨论了NSCLC亚型以及涉及DNA甲基化机制作为潜在癌症诊断和预后生物标志物的研究的当前趋势。由于DNMTs表达影响甲基化模式，我们的综述还概述了DNMTs的异常模式及其作为NSCLC潜在治疗靶点以恢复异常基因调控并产生更好预后的情况。
