Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
Stem Cells. 2013 Sep;31(9):1992-2002. doi: 10.1002/stem.1459.
Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.
已在多种上皮癌中观察到人类胚胎干细胞（hESC）特征基因的激活。在这项研究中，我们发现 hESC 特征在健康吸烟者的气道基底干细胞/祖细胞群体（BC-S）中被选择性诱导，其激活模式与所有主要类型的人类肺癌相似。我们进一步鉴定了一组 6 个 BC-S hESC 基因，它们在肺腺癌（AdCa）中的一致过表达与肺功能降低、分化程度较差、肿瘤分期较晚、生存时间显著缩短以及 TP53 突变频率较高相关。BC-S 与 hESC 和相当一部分肺癌共享一个共同的 TP53 失活分子模式，与 BC-S hESC 基因表达强烈相关。这些数据提供了基于转录组的证据，表明吸烟诱导气道 BC 向 hESC 样表型的重编程可能代表人类侵袭性肺癌发展中的一个常见早期分子事件。
