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Cancer Res. 2014 May 15;74(10):2892-902. doi: 10.1158/0008-5472.CAN-13-2775. Epub 2014 Mar 20.

A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma.

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1
Authors' Affiliations: Cancer Biology Program, Division of Hematology/Oncology, Department of Pediatrics; Center for Biomedical Informatics Research, Department of Medicine; Institute for Immunity, Transplant and Infection; Department of Cardiothoracic Surgery; and Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
2
Authors' Affiliations: Cancer Biology Program, Division of Hematology/Oncology, Department of Pediatrics; Center for Biomedical Informatics Research, Department of Medicine; Institute for Immunity, Transplant and Infection; Department of Cardiothoracic Surgery; and Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CaliforniaAuthors' Affiliations: Cancer Biology Program, Division of Hematology/Oncology, Department of Pediatrics; Center for Biomedical Informatics Research, Department of Medicine; Institute for Immunity, Transplant and Infection; Department of Cardiothoracic Surgery; and Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
3
Authors' Affiliations: Cancer Biology Program, Division of Hematology/Oncology, Department of Pediatrics; Center for Biomedical Informatics Research, Department of Medicine; Institute for Immunity, Transplant and Infection; Department of Cardiothoracic Surgery; and Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California ascor@stanford.edu abutte@stanford.edu.

Abstract

Lung cancer remains the most common cause of cancer-related death worldwide and it continues to lack effective treatment. The increasingly large and diverse public databases of lung cancer gene expression constitute a rich source of candidate oncogenic drivers and therapeutic targets. To define novel targets for lung adenocarcinoma, we conducted a large-scale meta-analysis of genes specifically overexpressed in adenocarcinoma. We identified an 11-gene signature that was overexpressed consistently in adenocarcinoma specimens relative to normal lung tissue. Six genes in this signature were specifically overexpressed in adenocarcinoma relative to other subtypes of non-small cell lung cancer (NSCLC). Among these genes was the little studied protein tyrosine kinase PTK7. Immunohistochemical analysis confirmed that PTK7 is highly expressed in primary adenocarcinoma patient samples. RNA interference-mediated attenuation of PTK7 decreased cell viability and increased apoptosis in a subset of adenocarcinoma cell lines. Further, loss of PTK7 activated the MKK7-JNK stress response pathway and impaired tumor growth in xenotransplantation assays. Our work defines PTK7 as a highly and specifically expressed gene in adenocarcinoma and a potential therapeutic target in this subset of NSCLC.

PMID:
24654231
PMCID:
PMC4084668
DOI:
10.1158/0008-5472.CAN-13-2775
[Indexed for MEDLINE]
Free PMC Article
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