Denisov Evgeny V, Schegoleva Anastasia A, Gerashchenko Tatiana S, Skryabin Nikolay A, Sleptcov Alexey A, Yakushina Valentina D, Lyapunova Liliya S, Tuzikov Sergey A, Pankova Olga V, Perelmuter Vladimir M
Tomsk National Research Medical Center.
Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk.
Appl Immunohistochem Mol Morphol. 2020 Jul;28(6):477-483. doi: 10.1097/PAI.0000000000000762.
The premalignant process preceding squamous cell lung cancer is not inevitable; it can stop at any of the bronchial lesions: basal cell hyperplasia (BCH), squamous metaplasia (SM), and dysplasia and then progress or regress. At present, the mechanisms underlying the progression of the bronchial lesions remain undefined. Previously, we hypothesized that bronchial lesions that presented individually or combined with each other in the bronchi of lung cancer patients mirror the different "scenarios" of the premalignant process: individual BCH-the stoppage at the stage of hyperplasia, BCH plus SM-the progression of hyperplasia to metaplasia, and SM plus dysplasia-the progression of metaplasia to dysplasia. In this study, we analyzed gene expression profiles of BCH, SM, and dysplasia depending on their cooccurrence in the bronchi of lung cancer patients. The immune response gene expression was found to be a key difference between the individual BCH and BCH combined with SM lesions and a potential mechanism that determines the progression of hyperplasia to metaplasia. Upregulation of the cell cycle and downregulation of the cilium assembly genes mainly distinguished SM that copresented with dysplasia from SM that copresented with BCH and is a probable mechanism of the progression of metaplasia to dysplasia. Dysplasia showed mainly overexpression of the cell division genes and underexpression of the inflammation genes. Thus, this study demonstrates the significant gene expression differences between the premalignant lesions depending on their cooccurrence in the bronchi and sheds light on the mechanisms of the precancerous process preceding squamous cell lung cancer.
肺鳞状细胞癌之前的癌前病变过程并非不可避免；它可以在任何一种支气管病变处停止：基底细胞增生（BCH）、鳞状化生（SM）和发育异常，然后进展或消退。目前，支气管病变进展的潜在机制仍不明确。此前，我们推测，在肺癌患者支气管中单独出现或相互组合出现的支气管病变反映了癌前病变过程的不同“情况”：单独的BCH——增生阶段的停止，BCH加SM——增生向化生的进展，以及SM加发育异常——化生向发育异常的进展。在本研究中，我们根据BCH、SM和发育异常在肺癌患者支气管中的同时出现情况分析了它们的基因表达谱。发现免疫反应基因表达是单独的BCH与BCH合并SM病变之间的关键差异，也是决定增生向化生进展的潜在机制。细胞周期的上调和纤毛组装基因的下调主要区分了与发育异常同时出现的SM和与BCH同时出现的SM，这可能是化生向发育异常进展的机制。发育异常主要表现为细胞分裂基因的过表达和炎症基因的低表达。因此，本研究证明了根据癌前病变在支气管中的同时出现情况，它们之间存在显著的基因表达差异，并揭示了肺鳞状细胞癌之前癌前病变过程的机制。
