Identification of HERC5 and its potential role in NSCLC progression. Issue 10 (9th November 2014)

• Record Type: Journal Article
• Authors: Wrage, Michaela; Hagmann, Wolfgang; Kemming, Dirk; Uzunoglu, Faik G.; Riethdorf, Sabine; Effenberger, Katharina; Westphal, Manfred; Lamszus, Katrin; Kim, Soo‐Zin; Becker, Natalia; Izbicki, Jakob R.; Sandoval, Juan; Esteller, Manel; Pantel, Klaus; Risch, Angela; Wikman, Harriet
• Is Part Of: International journal of cancer. Volume 136:Issue 10(2015:May 15)
• Page Start: 2264
• Page End: 2272
• Publication Date: 2014-11-09
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29298
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>For better lung cancer diagnosis and therapy, early detection markers of tumor dissemination are urgently needed, as most lung cancers do not show symptoms until extensive metastasis formation has already taken place. Our previous studies showed that in non‐small cell lung cancer (NSCLC) early tumor dissemination is associated with a loss of chromosome 4q12‐q32 and the presence of disseminated tumor cells (DTC) in the bone marrow. In order to identify the potential target gene in this region, a screen for methylation‐dependent expression was performed. Lung cancer cell lines showing a loss of 4q as well as a normal bronchial epithelial cell line as control were treated with 5‐aza‐2'‐deoxycytidine (5‐aza‐CdR) followed by expression profiling. Seven genes within the 4q target region, which have been associated with a positive DTC status before were found to be regulated by hypermethylation. QRT‐PCR in an independent sample set identified <italic>HERC5</italic> as a potential target gene. Quantitative methylation analysis of these lung tissue samples revealed that <italic>HERC5</italic> promoter hypermethylation was significantly associated with positive DTC status (<italic>p</italic> = 0.020) and occurrence of brain metastases (<italic>p</italic> = 0.015). In addition, hypermethylation of the <italic>HERC5</italic> promoter in NSCLC was identified as a predictor for poor survival for Stage I adenocarcinoma patients (<italic>p</italic> = 0.022) and also for poor overall survival in metastatic lung cancer patients (<italic>p</italic> = 0.028). In conclusion, <italic>HERC5</italic> may function as a prognostic marker and is associated with tumor dissemination in lung cancer.</p> </abstract>