title: Glycodelin: A New Biomarker with Immunomodulatory Functions in Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  In recent years, immune therapeutic strategies against non-small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer.
  
  
  METHODS
  In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments, and correlations with clinicopathologic parameters.
  
  
  RESULTS
  Glycodelin mRNA expression was significantly elevated in tumors (n = 336) compared with matched normal tissue (P < 0.0001). Overall survival (OS) was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, and the levels correlated with recurrence and metastatic disease. Knockdown of glycodelin with siRNAs in NSCLC cell lines resulted in significant upregulation of immune system modulatory factors such as PDL1, CXCL5, CXCL16, MICA/B, and CD83 as well as proliferation stimulators EDN1 and HBEGF. Furthermore, decreased migration of tumor cells was observed.
  
  
  CONCLUSIONS
  Altogether, the comprehensive characterization of glycodelin in NSCLC provides strong support for its use as a biomarker with immune modulatory function.
authors.affiliation: Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany. Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schneider
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Granzow
authors.affiliation: Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Institut für Allgemeine und Spezielle Pathologie, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.affiliation: Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. Department of Thoracic Oncology, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. Department of Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Felix J F
authors.initials: FJ
authors.lastname: Herth
authors.affiliation: Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. Department of Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.affiliation: Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany. Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.affiliation: Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany. Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. michael.meister@med.uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D000071816:Glycodelin; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D056747:Immunomodulation / Q000235:genetics*; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D000071816:Glycodelin; D006023:Glycoproteins; D009363:Neoplasm Proteins; C045246:PAEP protein, human; D012333:RNA, Messenger