Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Neoplasia. 2010 Jun;12(6):499-505. doi: 10.1593/neo.10390.
Increasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor-the G protein-coupled receptor 5A (Gprc5a). Microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice defined a loss-of-Gprc5a gene signature, which revealed many aberrations in cancer-associated pathways. To assess the relevance of this mouse tumor suppressor to human lung cancer, the loss-of-Gprc5a signature was cross species compared with and integrated with publicly available gene expression data of human normal lung tissue and non-small cell lung cancers. The loss-of-Gprc5a signature was prevalent in human lung adenocarcinomas compared with squamous cell carcinomas or normal lung. Furthermore, it identified subsets of lung adenocarcinomas with poor outcome. These results demonstrate that gene expression patterns of Gprc5a loss in nontumorigenic mouse lung epithelial cells are evolutionarily conserved and important in human lung adenocarcinomas.
提高对癌基因和抑癌基因变化影响的认识，对于改善肺癌的治疗至关重要。最近，我们鉴定了一种新的肺特异性抑癌基因——G 蛋白偶联受体 5A（Gprc5a）。对来自 Gprc5a 敲除和野生型小鼠正常气管的肺上皮细胞的转录组进行微阵列分析，确定了一个 Gprc5a 基因缺失特征，揭示了许多与癌症相关通路的异常。为了评估这种小鼠抑癌基因与人类肺癌的相关性，我们将缺失的 Gprc5a 特征与公开的人类正常肺组织和非小细胞肺癌的基因表达数据进行了跨物种比较和整合。与鳞状细胞癌或正常肺相比，缺失的 Gprc5a 特征在人肺腺癌中更为普遍。此外，它还鉴定出肺腺癌中预后不良的亚群。这些结果表明，在非致瘤性的小鼠肺上皮细胞中，Gprc5a 缺失的基因表达模式在进化上是保守的，并且在人类肺腺癌中非常重要。
