title: DNA methylation transcriptionally regulates the putative tumor cell growth suppressor ZNF677 in non-small cell lung cancers.
abstract: In our study, we investigated the role of ZNF677 in non-small cell lung cancers (NSCLC). By comparing ZNF677 expression in primary tumor (TU) and in the majority of cases also of corresponding non-malignant lung tissue (NL) samples from > 1,000 NSCLC patients, we found tumor-specific downregulation of ZNF677 expression (adjusted p-values < 0.001). We identified methylation as main mechanism for ZNF677 downregulation in NSCLC cells and we observed tumor-specific ZNF677 methylation in NSCLC patients (p < 0.0001). In the majority of TUs, ZNF677 methylation was associated with loss of ZNF677 expression. Moreover, ZNF677 overexpression in NSCLC cells was associated with reduced cell proliferation and cell migration. ZNF677 was identified to regulate expression of many genes mainly involved in growth hormone regulation and interferon signalling. Finally, patients with ZNF677 methylated TUs had a shorter overall survival compared to patients with ZNF677 not methylated TUs (p = 0.013). Overall, our results demonstrate that ZNF677 is trancriptionally regulated by methylation in NSCLCs, suggest that ZNF677 has tumor cell growth suppressing properties in NSCLCs and that ZNF677 methylation might serve as prognostic parameter in these patients.
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerwin
authors.initials: G
authors.lastname: Heller
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Corinna
authors.initials: C
authors.lastname: Altenberger
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schmid
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Marhold
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tomasich
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziegler
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Müllauer
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Minichsdorfer
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Lang
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Adelheid
authors.initials: A
authors.lastname: End-Pfützenreuter
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary. Department of Thoracic Oncology and Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Döme
authors.affiliation: Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria.
authors.forename: Britt-Madeleine
authors.initials: BM
authors.lastname: Arns
authors.affiliation: University of Queensland, The Prince Charles Hospital, Queensland, Chermside, Australia.
authors.forename: Kwun M
authors.initials: KM
authors.lastname: Fong
authors.affiliation: University of Queensland, The Prince Charles Hospital, Queensland, Chermside, Australia.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Wright
authors.affiliation: University of Queensland, The Prince Charles Hospital, Queensland, Chermside, Australia.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Zöchbauer-Müller
mesh_terms: D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D046888:Tissue Array Analysis; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics*