Abstract LB-129: CAFET algorithm reveals WNT/PCP specific signature in squamous cell carcinoma of lung cancer

Abstract

Abstract We analyzed the global gene expression patterns of 138 lung cancer samples containing Squamous Cell Carcinoma (SCC) and Adenocarcinoma (AC). Gene set enrichment analysis revealed developmental and cell cycle functional groups were specifically overexpressed in SCC samples. To refine and focus our analysis on specific signaling pathways, we developed a complementary algorithm called Coverage Analysis with Fisher Exact Test (CAFET). In our analysis, the WNT signaling pathway had the most significant enrichment of overexpressed genes in a cluster of predominantly SCC. Most interestingly, the differential expression pattern in this cluster had a strong tendency to inhibit the WNT canonical pathway while enhancing the WNT/PCP pathway. The non-canonical WNT/PCP pathway is obligatory for cell migration during embryogenesis, and it has also been proposed to be involved in cancer metastasis. While the WNT canonical pathway has been reported to be important in metastasis of AC in lung cancer, our results suggest SCC of lung makes use of a different branch of the WNT pathway for survival and development. This WNT/PCP signature for lung SCC was also confirmed in several independent sample sets. It is also present in some cell lines derived from lung SCC. To find potential clinical biomarkers, we identified 174 genes present in blood and highly expressed in samples carrying this WNT/PCP signature. These results demonstrate that the new algorithm CAFET is a promising approach for mining large gene expression data sets to identify pathways with differential activity, and could be particularly useful in exploring cancer expression datasets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-129.