Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2010 Feb 9;5(2):e9112. doi: 10.1371/journal.pone.0009112.
Non-small cell lung cancer (NSCLC) represents the majority (85%) of lung cancers and is comprised mainly of adenocarcinomas and squamous cell carcinomas (SCCs). The sequential pathogenesis of lung adenocarcinomas and SCCs occurs through dissimilar phases as the former tumors typically arise in the lung periphery whereas the latter normally arise near the central airway.
METHODOLOGY/PRINCIPAL FINDINGS: We assessed the expression of SOX2, an embryonic stem cell transcriptional factor that also plays important roles in the proliferation of basal tracheal cells and whose expression is restricted to the main and central airways and bronchioles of the developing and adult mouse lung, in NSCLC by various methodologies. Here, we found that SOX2 mRNA levels, from various published datasets, were significantly elevated in lung SCCs compared to adenocarcinomas (all p<0.001). Moreover, a previously characterized OCT4/SOX2/NANOG signature effectively separated lung SCCs from adenocarcinomas in two independent publicly available datasets which correlated with increased SOX2 mRNA in SCCs. Immunohistochemical analysis of various histological lung tissue specimens demonstrated marked nuclear SOX2 protein expression in all normal bronchial epithelia, alveolar bronchiolization structures and premalignant lesions in SCC development (hyperplasia, dysplasia and carcinoma in situ) and absence of expression in all normal alveoli and atypical adenomatous hyperplasias. Moreover, SOX2 protein expression was greatly higher in lung SCCs compared to adenocarcinomas following analyses in two independent large TMA sets (TMA set I, n = 287; TMA set II, n = 511 both p<0.001). Furthermore, amplification of SOX2 DNA was detected in 20% of lung SCCs tested (n = 40) and in none of the adenocarcinomas (n = 17).
CONCLUSIONS/SIGNIFICANCE: Our findings highlight a cell-lineage gene expression pattern for the stem cell transcriptional factor SOX2 in the pathogenesis of lung SCCs and suggest a differential activation of stem cell-related pathways between squamous cell carcinomas and adenocarcinomas of the lung.
非小细胞肺癌（NSCLC）占肺癌的大多数（85%），主要由腺癌和鳞状细胞癌（SCC）组成。肺腺癌和 SCC 的连续发病机制发生在不同的阶段，因为前者肿瘤通常起源于肺外周，而后者通常起源于中央气道附近。
方法/主要发现：我们通过各种方法评估了 SOX2 的表达，SOX2 是一种胚胎干细胞转录因子，在基底气管细胞的增殖中也发挥重要作用，其表达仅限于发育中和成年小鼠肺的主要和中央气道以及细支气管。在这里，我们发现，从各种已发表的数据集来看，SOX2 mRNA 水平在肺 SCC 中明显高于腺癌（均 p<0.001）。此外，一个以前被描述的 OCT4/SOX2/NANOG 特征有效地将肺 SCC 与两个独立的公开可用数据集的腺癌区分开来，这与 SCC 中 SOX2 mRNA 的增加相关。对各种组织学肺组织标本的免疫组织化学分析显示，所有正常支气管上皮、肺泡细支气管化结构和 SCC 发展中的癌前病变（增生、发育不良和原位癌）中均有明显的核 SOX2 蛋白表达，而所有正常肺泡和非典型腺瘤性增生中均无表达。此外，在两个独立的大型 TMA 集（TMA 集 I，n=287；TMA 集 II，n=511）中，SOX2 蛋白表达在肺 SCC 中明显高于腺癌（均 p<0.001）。此外，在检测到的 20%的肺 SCC（n=40）中检测到 SOX2 DNA 扩增，而在腺癌中均未检测到（n=17）。
结论/意义：我们的研究结果突出了转录因子 SOX2 在肺 SCC 发病机制中的细胞谱系基因表达模式，并表明肺 SCC 和腺癌之间的干细胞相关途径的激活存在差异。
