Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Bull Exp Biol Med. 2024 May;177(1):93-97. doi: 10.1007/s10517-024-06138-4. Epub 2024 Jul 4.
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.
鳞状细胞肺癌 (SCLC) 是由于支气管上皮的退行性变化而发生的：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 患者的小支气管中检测到的癌前变化的组合可能反映了癌前过程的各种“情况”：孤立的 BCH→停留在增生阶段，BCH+SM→增生进展为化生，SM+发育不良→化生进展为发育不良。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的癌前变化的 DNA 甲基组。在 BCH 合并 SM 的情况下，与孤立的 BCH 相比，在具有重要病理意义的 MET 信号通路（RNMT、HPN）的基因中鉴定出差异甲基化区域。与 BCH 合并 SM 相比，在 SM 合并发育不良中检测到影响炎症调节基因（IL-23、IL-23R、IL12B、IL12RB1 和 FIS1）的差异甲基化区域。DNA 甲基化的这些变化可能是支气管上皮癌前过程各种“情况”的基础。
