title: Prognostic impact of COX-2 in non-small cell lung cancer: a comprehensive compartment-specific evaluation of tumor and stromal cell expression.
abstract: Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n = 1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n = 616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johanna S M
authors.initials: JS
authors.lastname: Mattsson
authors.affiliation: Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Bergman
authors.affiliation: Department of Statistics, TU Dortmund University, Dortmund, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Grinberg
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), TU Dortmund University.
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Millaray
authors.initials: M
authors.lastname: Marincevic
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), TU Dortmund University.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Department of Statistics, TU Dortmund University, Dortmund, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Department of Pathology, Örebro University Hospital, Örebro University, Örebro, Sweden.
authors.forename: Mats G
authors.initials: MG
authors.lastname: Karlsson
authors.affiliation: Department of Pathology, Örebro University Hospital, Örebro University, Örebro, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Karlsson
authors.affiliation: Department of Pathology, Örebro University Hospital, Örebro University, Örebro, Sweden.
authors.forename: Gisela
authors.initials: G
authors.lastname: Helenius
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Electronic address: patrick.micke@igp.uu.se.
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Miklos
authors.initials: M
authors.lastname: Gulyas
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Cyclooxygenase 2; Immunohistochemistry; Lung cancer; Microarray; PTGS2; Prognosis