Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
National Research Tomsk State University, Tomsk, Russia.
Mol Biol Rep. 2023 Sep;50(9):7941-7947. doi: 10.1007/s11033-023-08571-6. Epub 2023 Jul 22.
Squamous cell lung cancer (SCLC) arises from bronchial changes: basal cell hyperplasia (BCH), squamous metaplasia (SM), and dysplasia. However, the premalignant process preceding SCLC is not inevitable; it can stop at any of the bronchial lesions. Previously, we hypothesized that combinations of premalignant lesions observed in the small bronchi of SCLC patients can reflect the different "scenarios" of the premalignant process: BCH-the stoppage at the stage of hyperplasia and BCH-the progression of hyperplasia to metaplasia.
In this study, using whole-genome bisulfite sequencing we analyzed the DNA methylome of two forms of BCH: isolated BCH (BCH) and BCH co-occurred with SM (BCH) in the small bronchi of SCLC patients. It was shown that BCH harbored differentially methylated regions (DMRs) affecting genes associated with regulating phosphatase activity. In BCH, DMRs were found in genes involved in PI3K-Akt and AMPK signaling pathways. DMRs were also found to affect specific miRNA genes: miR-34a and miR-3648 in BCH and miR-924 and miR-100 in BCH.
Thus, this study demonstrated the significant changes in DNA methylome between the isolated BCH and BCH combined with SM. The identified epigenetic alterations may underlie different "scenarios" of the premalignant process in the bronchial epithelium.
鳞状细胞肺癌（SCLC）源自支气管改变：基底细胞增生（BCH）、鳞状化生（SM）和发育不良。然而，SCLC 之前的癌前病变过程并非不可避免；它可以在任何支气管病变处停止。此前，我们假设在 SCLC 患者的小支气管中观察到的癌前病变组合可以反映癌前病变过程的不同“场景”：BCH-在增生阶段停止和 BCH-增生向化生的进展。
在这项研究中，我们使用全基因组亚硫酸氢盐测序分析了两种形式的 BCH 的 DNA 甲基组：孤立的 BCH（BCH）和 BCH 与 SCLC 患者小支气管中的 SM 共存（BCH）。结果表明，BCH 具有影响调节磷酸酶活性相关基因的差异甲基化区域（DMR）。在 BCH 中，DMR 存在于参与 PI3K-Akt 和 AMPK 信号通路的基因中。DMR 还被发现影响特定的 miRNA 基因：BCH 中的 miR-34a 和 miR-3648 以及 BCH 中的 miR-924 和 miR-100。
因此，这项研究表明孤立的 BCH 和与 SM 结合的 BCH 之间的 DNA 甲基组发生了显著变化。所确定的表观遗传改变可能是支气管上皮不同“场景”的癌前病变过程的基础。
