肺癌是全球癌症死亡的主要原因，每年夺去约180万人的生命。传统的诊断方法如影像学和组织活检虽然重要，但在理解疾病的分子本质方面存在显著局限性。癌症涉及复杂的基因和表观遗传变化，这些变化无法通过常规方法完全捕获。这促使了分子检测方法的发展，能够提供对癌症生物学更深入的见解。
DNA甲基化是一种重要的表观遗传修饰机制。它不改变DNA的序列，但通过在胞嘧啶碱基上添加甲基基团来影响基因的表达。在癌症的发生发展过程中，DNA甲基化起着关键作用。异常的甲基化模式可以导致肿瘤抑制基因的沉默，从而促进癌症的发生。
肺癌甲基化检测采用多种先进的分子生物学方法。主要包括亚硫酸氢盐测序法、甲基化特异性PCR、焦磷酸测序法和甲基化芯片技术。检测过程通常从血液或组织样本开始，提取DNA后进行甲基化分析，这些方法能够精确检测DNA甲基化水平。
肺癌甲基化检测在临床医学中具有重要价值。它能够实现早期诊断和筛查，帮助医生在疾病早期发现癌症。同时，甲基化检测还能进行预后评估和风险分层，为治疗方案的个体化选择提供依据。此外，它还可用于疗效监测和随访，为精准医疗的实施提供科学依据。
DNA methylation is a crucial epigenetic mechanism that regulates gene expression. It involves the addition of methyl groups to cytosine bases, particularly in CpG dinucleotides. This modification acts like an on-off switch for genes, controlling their activity without altering the underlying DNA sequence. When genes are methylated, they are typically silenced, while unmethylated genes remain active. This process is essential for normal cellular function and development.
In cancer development, abnormal hypermethylation patterns emerge at tumor suppressor gene promoters. This hypermethylation leads to the silencing of crucial genes that normally protect cells from becoming cancerous. In lung cancer, key genes affected by hypermethylation include CDKN2A slash p16, which controls cell cycle progression, MLH1 involved in DNA repair, and MGMT which repairs DNA damage. When these protective genes are silenced through methylation, cells lose their natural defenses against cancer development.
Several sophisticated laboratory techniques are employed to detect DNA methylation patterns. The main methods include bisulfite sequencing, methylation-specific PCR, pyrosequencing, and methylation arrays. The key principle underlying most of these techniques is bisulfite treatment, which chemically converts unmethylated cytosines to uracil while leaving methylated cytosines unchanged. This chemical difference allows researchers to distinguish between methylated and unmethylated DNA regions through subsequent PCR amplification and sequencing analysis.
Methylation testing has proven invaluable in clinical lung cancer management across multiple domains. For diagnostic classification, it helps distinguish between different cancer subtypes and origins. In prognostic assessment, methylation patterns provide crucial information about patient outcomes and disease progression. Treatment selection is significantly enhanced, particularly with MGMT methylation status influencing the effectiveness of alkylating agent therapies. The technology also enables continuous therapy response monitoring. Sample collection has evolved to include both traditional tissue biopsies and innovative liquid biopsies, which offer non-invasive testing options for patients.