A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma.
By: Ron Chen, Purvesh Khatri, Pawel K Mazur, Melanie Polin, Yanyan Zheng, Dedeepya Vaka, Chuong D Hoang, Joseph Shrager, Yue Xu, Silvestre Vicent, Atul Butte, E Alejandro Sweet-Cordero

Pediatrics, Stanford Univesity.
2014-3-22; doi: 10.1158/0008-5472.CAN-13-2775
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 (ADC), we conducted a large scale meta-analysis of genes specifically overexpressed in ADC. We identified an eleven-gene signature that was overexpressed consistently in ADC specimens relative to normal lung tissue. Six genes in this signature were specifically overexpressed in ADC 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 ADC patient samples. RNAi-mediated attenuation of PTK7 decreased cell viability and increased apoptosis in a subset of ADC 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 ADC and a potential therapeutic target in this subset of NSCLC.





PMID:24654231






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