鳞状细胞肺癌 (SCLC) 是支气管上皮再生异常的结果：基底细胞增生 (BCH)、鳞状细胞化生 (SM) 和发育不良。我们之前提出，在SCLC患者小支气管中检测到的癌前变化组合可能反映了癌前过程的各种“场景”：孤立的BCH→停止于增生阶段，BCH SM→增生进展为化生，SM发育不良→化生进展为不典型增生。在这项研究中，使用全基因组亚硫酸氢盐测序分析了 SCLC 患者支气管上皮中各种形式癌前变化的 DNA 甲基化组。在 BCH 与 SM 组合中，与单独的 BCH 相比，在具有致病意义的 MET 信号通路（RNMT、HPN）的基因中发现了差异甲基化区域。与SM联合BCH相比，在SM联合不典型增生中检测到影响炎症调节相关基因（IL-23、IL-23R、IL12B、IL12RB1和FIS1）的差异甲基化区域。 DNA 甲基化的揭示变化可能是支气管上皮癌前过程的各种“场景”的基础。© 2024。Springer Science Business Media, LLC，Springer Nature 旗下公司。

Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various "scenarios" of the precancerous process: isolated BCH→stopping at the stage of hyperplasia, BCH+SM→progression of hyperplasia into metaplasia, SM+dysplasia→progression of metaplasia into dysplasia. In this study, DNA methylome of various forms of precancerous changes in the bronchial epithelium of SCLC patients was analyzed using the genome-wide bisulfite sequencing. In BCH combined with SM, in contrast to isolated BCH, differentially methylated regions were identified in genes of the pathogenetically significant MET signaling pathway (RNMT, HPN). Differentially methylated regions affecting genes involved in inflammation regulation (IL-23, IL-23R, IL12B, IL12RB1, and FIS1) were detected in SM combined with dysplasia in comparison with SM combined with BCH. The revealed changes in DNA methylation may underlie various "scenarios" of the precancerous process in the bronchial epithelium.© 2024. Springer Science+Business Media, LLC, part of Springer Nature.