TY  - JOUR
AU  - Wrage, Michaela
AU  - Hagmann, Wolfgang
AU  - Kemming, Dirk
AU  - Uzunoglu, Faik G
AU  - Riethdorf, Sabine
AU  - Effenberger, Katharina
AU  - Westphal, Manfred
AU  - Lamszus, Katrin
AU  - Kim, Soo-Zin
AU  - Becker, Natalia
AU  - Izbicki, Jakob R
AU  - Sandoval, Juan
AU  - Esteller, Manel
AU  - Pantel, Klaus
AU  - Risch, Angela
AU  - Wikman, Harriet
TI  - Identification of HERC5 and its potential role in NSCLC progression.
JO  - International journal of cancer
VL  - 136
IS  - 10
SN  - 0020-7136
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2017-03834
SP  - 2264 - 2272
PY  - 2015
AB  - 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 HERC5 as a potential target gene. Quantitative methylation analysis of these lung tissue samples revealed that HERC5 promoter hypermethylation was significantly associated with positive DTC status (p = 0.020) and occurrence of brain metastases (p = 0.015). In addition, hypermethylation of the HERC5 promoter in NSCLC was identified as a predictor for poor survival for Stage I adenocarcinoma patients (p = 0.022) and also for poor overall survival in metastatic lung cancer patients (p = 0.028). In conclusion, HERC5 may function as a prognostic marker and is associated with tumor dissemination in lung cancer.
KW  - HERC5 protein, human (NLM Chemicals)
KW  - Intracellular Signaling Peptides and Proteins (NLM Chemicals)
KW  - decitabine (NLM Chemicals)
KW  - Azacitidine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25353388
DO  - DOI:10.1002/ijc.29298
UR  - https://inrepo02.dkfz.de/record/127812
ER  -