Supplemental Digital Content is available in the text. 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.

中文翻译：

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基因表达谱揭示了两种具有不同进展潜能的支气管基底细胞增生和鳞状上皮化生

补充数字内容在文本中可用。鳞状细胞肺癌之前的癌前过程并非不可避免；它可以在任何支气管病变处停止：基底细胞增生 (BCH)、鳞状上皮化生 (SM) 和发育不良，然后进展或消退。目前，支气管病变进展的机制仍未明确。此前，我们假设肺癌患者支气管中单独或相互结合的支气管病变反映了癌前过程的不同“场景”：个体BCH——增生阶段的停止，BCH加SM——进展增生到化生，以及 SM 加不典型增生——化生到不典型增生的进展。在本研究中，我们分析了 BCH、SM、和不典型增生取决于它们在肺癌患者支气管中的共同发生。发现免疫反应基因表达是个体 BCH 和 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不良共同呈递的 SM 与与 BCH 共同呈递的 SM，并且是化生向发育不良进展的可能机制。发育不良主要表现为细胞分裂基因的过度表达和炎症基因的低表达。因此，