原创力文档cafet algorithm reveals wntpcp signature in lung squamous cell carcinomacafet算法揭示wntpcp签名在肺鳞状细胞癌.pdfVIP
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cafet algorithm reveals wntpcp signature in lung squamous cell carcinomacafet算法揭示wntpcp签名在肺鳞状细胞癌
CAFET Algorithm Reveals Wnt/PCP Signature in Lung
Squamous Cell Carcinoma
Yue Hu¤a, Anna V. Galkin, Chunlei Wu¤b, Venkateshwar Reddy¤c, Andrew I. Su*¤b
Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America
Abstract
We analyzed the gene expression patterns of 138 Non-Small Cell Lung Cancer (NSCLC) samples and developed a new
algorithm called Coverage Analysis with Fisher’s Exact Test (CAFET) to identify molecular pathways that are differentially
activated in squamous cell carcinoma (SCC) and adenocarcinoma (AC) subtypes. Analysis of the lung cancer samples
demonstrated hierarchical clustering according to the histological subtype and revealed a strong enrichment for the Wnt
signaling pathway components in the cluster consisting predominantly of SCC samples. The specific gene expression
pattern observed correlated with enhanced activation of the Wnt Planar Cell Polarity (PCP) pathway and inhibition of the
canonical Wnt signaling branch. Further real time RT-PCR follow-up with additional primary tumor samples and lung cancer
cell lines confirmed enrichment of Wnt/PCP pathway associated genes in the SCC subtype. Dysregulation of the canonical
Wnt pathway, characterized by increased levels of b-catenin and epigenetic silencing of negative regulators, has been
reported in adenocarcinoma of the lung. Our results suggest that SCC and AC utilize different branches of the Wnt pathway
during oncogenesis.
Citation: Hu Y, Galkin AV, Wu C, Reddy V, Su AI (2011) CAFET Algorithm Reveals Wnt/PCP Signature in Lung Squamous Cell Carcinoma. PLoS ONE 6(10): e25807.
doi:10.1371/journal.pone.0025807
Editor: John D. Minna, Univesity of Texas Southwestern Medical Center at Dallas, United States of America
Received March 16, 2011; Accepted September 12, 2011; Published October 10, 2011
Co
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