title: Overexpression of GPC6 and TMEM132D in Early Stage Ovarian Cancer Correlates with CD8+ T-Lymphocyte Infiltration and Increased Patient Survival.
abstract: Infiltration of cytotoxic T-lymphocytes in ovarian cancer is a favorable prognostic factor. Employing a differential expression approach, we have recently identified a number of genes associated with CD8+ T-cell infiltration in early stage ovarian tumors. In the present study, we validated by qPCR the expression of two genes encoding the transmembrane proteins GPC6 and TMEM132D in a cohort of early stage ovarian cancer patients. The expression of both genes correlated positively with the mRNA levels of CD8A, a marker of T-lymphocyte infiltration [Pearson coefficient: 0.427 (p = 0.0067) and 0.861 (p < 0.0001), resp.]. GPC6 and TMEM132D expression was also documented in a variety of ovarian cancer cell lines. Importantly, Kaplan-Meier survival analysis revealed that high mRNA levels of GPC6 and/or TMEM132D correlated significantly with increased overall survival of early stage ovarian cancer patients (p = 0.032). Thus, GPC6 and TMEM132D may serve as predictors of CD8+ T-lymphocyte infiltration and as favorable prognostic markers in early stage ovarian cancer with important consequences for diagnosis, prognosis, and tumor immunobattling.
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karapetsas
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece ; Division of Genome and Gene Expression Data Analysis, Bioinformatics Institute, Agency for Science, Technology and Research (A∗STAR), Singapore 138671.
authors.forename: Antonis
authors.initials: A
authors.lastname: Giannakakis
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece ; Department of Oncology, University Hospital of Lausanne (CHUV), Ludwig Cancer Research Center, University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Denarda
authors.initials: D
authors.lastname: Dangaj
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece ; Department of Oncology, University Hospital of Lausanne (CHUV), Ludwig Cancer Research Center, University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Evripidis
authors.initials: E
authors.lastname: Lanitis
authors.affiliation: Laboratory of Histology and Embryology, School of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Kynigopoulos
authors.affiliation: Laboratory of Histology and Embryology, School of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Lambropoulou
authors.affiliation: Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, PA 19014, USA.
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Alex
authors.initials: A
authors.lastname: Galanis
authors.affiliation: Department of Clinical Oncology, School of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.affiliation: Medical Statistics Lab, School of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Gregorios
authors.initials: G
authors.lastname: Trypsianis
authors.affiliation: Department of Oncology, University Hospital of Lausanne (CHUV), Ludwig Cancer Research Center, University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.affiliation: Laboratory of Gene Expression, Molecular Diagnosis and Modern Therapeutics, Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Raphael
authors.initials: R
authors.lastname: Sandaltzopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053673:Glypicans / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D010414:Pennsylvania / Q000453:epidemiology; D015995:Prevalence; D012307:Risk Factors; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C120300:GPC6 protein, human; D053673:Glypicans; D008565:Membrane Proteins; C580886:TMEM132D protein, human