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000826699 1001_ $$0P:(DE-HGF)0$$aSchlensog, Martin$$b0
000826699 245__ $$aEpigenetic loss of putative tumor suppressor SFRP3 correlates with poor prognosis of lung adenocarcinoma patients
000826699 260__ $$aAustin, Tex.$$bLandes Bioscience$$c2018
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000826699 520__ $$aSecreted frizzled related protein 3 (SFRP3) contains a cysteine-rich domain (CRD) that shares homology with Frizzled CRD and regulates WNT signaling. Independent studies showed epigenetic silencing of SFRP3 in melanoma and hepatocellular carcinoma. Moreover, a tumor suppressive function of SFRP3 was shown in androgen-independent prostate and gastric cancer cells. The current study is the first to investigate SFRP3 expression and its potential clinical impact on non-small cell lung carcinoma (NSCLC). WNT signaling components present on NSCLC subtypes were preliminary elucidated by expression data of The Cancer Genome Atlas (TCGA). We identified a distinct expression signature of relevant WNT signaling components that differ between adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Of interest, canonical WNT signaling is predominant in LUAD samples and non-canonical WNT signaling is predominant in LUSC. In line, high SFRP3 expression resulted in beneficial clinical outcome for LUAD but not for LUSC patients. Furthermore, SFRP3 mRNA expression was significantly decreased in NSCLC tissue compared to normal lung samples. TCGA data verified the reduction of SFRP3 in LUAD and LUSC patients. Moreover, DNA hypermethylation of SFRP3 was evaluated in the TCGA methylation dataset resulting in epigenetic inactivation of SFRP3 expression in LUAD, but not in LUSC, and was validated by pyrosequencing of our NSCLC tissue cohort and in vitro demethylation experiments. Immunohistochemistry confirmed SFRP3 protein downregulation in primary NSCLC and indicated ...
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000826699 7001_ $$0P:(DE-HGF)0$$aMagnus, Lara$$b1
000826699 7001_ $$0P:(DE-HGF)0$$aHeide, Timon$$b2
000826699 7001_ $$0P:(DE-Juel1)174333$$aEschenbruch, Julian$$b3
000826699 7001_ $$0P:(DE-HGF)0$$aSteib, Florian$$b4
000826699 7001_ $$0P:(DE-HGF)0$$aTator, Maximilian$$b5
000826699 7001_ $$0P:(DE-HGF)0$$aKloten, Vera$$b6
000826699 7001_ $$0P:(DE-HGF)0$$aRose, Michael$$b7
000826699 7001_ $$0P:(DE-Juel1)145698$$aNoetzel, Erik$$b8
000826699 7001_ $$0P:(DE-HGF)0$$aGaisa, Nadine T.$$b9
000826699 7001_ $$0P:(DE-HGF)0$$aKnüchel, Ruth$$b10
000826699 7001_ $$0P:(DE-HGF)0$$aDahl, Edgar$$b11$$eCorresponding author
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