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000127812 1001_ $$aWrage, Michaela$$b0
000127812 245__ $$aIdentification of HERC5 and its potential role in NSCLC progression.
000127812 260__ $$aBognor Regis$$bWiley-Liss$$c2015
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000127812 520__ $$aFor better lung cancer diagnosis and therapy, early detection markers of tumor dissemination are urgently needed, as most lung cancers do not show symptoms until extensive metastasis formation has already taken place. Our previous studies showed that in non-small cell lung cancer (NSCLC) early tumor dissemination is associated with a loss of chromosome 4q12-q32 and the presence of disseminated tumor cells (DTC) in the bone marrow. In order to identify the potential target gene in this region, a screen for methylation-dependent expression was performed. Lung cancer cell lines showing a loss of 4q as well as a normal bronchial epithelial cell line as control were treated with 5-aza-2'-deoxycytidine (5-aza-CdR) followed by expression profiling. Seven genes within the 4q target region, which have been associated with a positive DTC status before were found to be regulated by hypermethylation. QRT-PCR in an independent sample set identified HERC5 as a potential target gene. Quantitative methylation analysis of these lung tissue samples revealed that HERC5 promoter hypermethylation was significantly associated with positive DTC status (p = 0.020) and occurrence of brain metastases (p = 0.015). In addition, hypermethylation of the HERC5 promoter in NSCLC was identified as a predictor for poor survival for Stage I adenocarcinoma patients (p = 0.022) and also for poor overall survival in metastatic lung cancer patients (p = 0.028). In conclusion, HERC5 may function as a prognostic marker and is associated with tumor dissemination in lung cancer.
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000127812 650_7 $$2NLM Chemicals$$aHERC5 protein, human
000127812 650_7 $$2NLM Chemicals$$aIntracellular Signaling Peptides and Proteins
000127812 650_7 $$0776B62CQ27$$2NLM Chemicals$$adecitabine
000127812 650_7 $$0M801H13NRU$$2NLM Chemicals$$aAzacitidine
000127812 7001_ $$0P:(DE-HGF)0$$aHagmann, Wolfgang$$b1
000127812 7001_ $$aKemming, Dirk$$b2
000127812 7001_ $$aUzunoglu, Faik G$$b3
000127812 7001_ $$aRiethdorf, Sabine$$b4
000127812 7001_ $$aEffenberger, Katharina$$b5
000127812 7001_ $$aWestphal, Manfred$$b6
000127812 7001_ $$aLamszus, Katrin$$b7
000127812 7001_ $$aKim, Soo-Zin$$b8
000127812 7001_ $$0P:(DE-He78)ecb33fb615e08035fdcefcaebfdff8f0$$aBecker, Natalia$$b9$$udkfz
000127812 7001_ $$aIzbicki, Jakob R$$b10
000127812 7001_ $$aSandoval, Juan$$b11
000127812 7001_ $$aEsteller, Manel$$b12
000127812 7001_ $$aPantel, Klaus$$b13
000127812 7001_ $$0P:(DE-He78)4981f4ef151aea881f38b33df8e35a21$$aRisch, Angela$$b14$$udkfz
000127812 7001_ $$aWikman, Harriet$$b15
000127812 773__ $$0PERI:(DE-600)1474822-8$$a10.1002/ijc.29298$$gVol. 136, no. 10, p. 2264 - 2272$$n10$$p2264 - 2272$$tInternational journal of cancer$$v136$$x0020-7136$$y2015
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