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CAFET 算法揭示肺鳞癌中的 Wnt/PCP 特征。

CAFET algorithm reveals Wnt/PCP signature in lung squamous cell carcinoma.

机构信息

Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America.

出版信息

PLoS One. 2011;6(10):e25807. doi: 10.1371/journal.pone.0025807. Epub 2011 Oct 10.

DOI:10.1371/journal.pone.0025807
PMID:22016777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3189939/
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 β-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.

摘要

我们分析了 138 个非小细胞肺癌 (NSCLC) 样本的基因表达模式，并开发了一种名为 Fisher 精确检验覆盖分析 (CAFET) 的新算法，以识别在鳞状细胞癌 (SCC) 和腺癌 (AC) 亚型中差异激活的分子途径。对肺癌样本的分析根据组织学亚型进行了层次聚类，并揭示了在主要由 SCC 样本组成的聚类中强烈富集的 Wnt 信号通路成分。观察到的特定基因表达模式与 Wnt 平面细胞极性 (PCP) 途径的增强激活和经典 Wnt 信号分支的抑制相关。进一步用额外的原发性肿瘤样本和肺癌细胞系进行实时 RT-PCR 随访，证实 SCC 亚型中富集了 Wnt/PCP 途径相关基因。经典 Wnt 通路的失调，表现为 β-连环蛋白水平升高和负调节剂的表观遗传沉默，已在肺腺癌中报道。我们的结果表明，SCC 和 AC 在癌变过程中利用 Wnt 通路的不同分支。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/6d28341ac679/pone.0025807.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/df7be0a5b26c/pone.0025807.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/50c92499721d/pone.0025807.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/9c3205addf6e/pone.0025807.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/e255fcd1d6b7/pone.0025807.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/6d28341ac679/pone.0025807.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/df7be0a5b26c/pone.0025807.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/50c92499721d/pone.0025807.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/9c3205addf6e/pone.0025807.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/e255fcd1d6b7/pone.0025807.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f73/3189939/6d28341ac679/pone.0025807.g005.jpg

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