title: GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma.
abstract: GASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adenocarcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma.
authors.affiliation: Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, and Imaging Center, Department of Clinical pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Uimonen
authors.affiliation: Institute of Clinical Medicine, Department of Internal Medicine, Respiratory Unit, Centre of Excellence in Research, University of Oulu, Oulu, Finland.
authors.forename: Heta
authors.initials: H
authors.lastname: Merikallio
authors.affiliation: Department of Pathology, Oulu University Hospital, Oulu, Finland.
authors.forename: Paavo
authors.initials: P
authors.lastname: Pääkkö
authors.affiliation: Institute of Clinical Medicine, Department of Internal Medicine, Respiratory Unit, Centre of Excellence in Research, University of Oulu, Oulu, Finland.
authors.forename: Terttu
authors.initials: T
authors.lastname: Harju
authors.affiliation: Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, and Imaging Center, Department of Clinical pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Palvimo
authors.affiliation: Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, and Imaging Center, Department of Clinical pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.affiliation: Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, and Imaging Center, Department of Clinical pathology, Kuopio University Hospital, Kuopio, Finland. ylermi.soini@uef.fi.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012907:Smoking / Q000378:metabolism* / Q000473:pathology
chemical_list: C413655:KDM4C protein, human; D056484:Jumonji Domain-Containing Histone Demethylases