title: CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome.
abstract: Malignant mesothelioma is a deadly tumor whose diagnosis and treatment remain very challenging. There is an urgent need to advance our understanding of mesothelioma biology and to identify new molecular markers for improving management of patients. CD157 is a membrane glycoprotein linked to ovarian cancer progression and mesenchymal differentiation. The common embryonic origin of ovarian epithelial cells and mesothelial cells and the evident similarities between ovarian and mesothelial cancer prompted us to investigate the biological role and clinical significance of CD157 in malignant pleural mesothelioma (MPM). CD157 mRNA and protein were detected in four of nine MPM cell lines of diverse histotype and in 85.2% of MPM surgical tissue samples (32/37 epithelioid; 37/44 biphasic). CD157 expression correlated with clinical aggressiveness in biphasic MPM. Indeed, high CD157 was a negative prognostic factor and an independent predictor of poor survival for patients with biphasic MPM by multivariate survival analysis (HR = 2.433, 95% CI 1.120-5.284; p = 0.025). In mesothelioma cell lines, CD157 gain (in CD157-negative cells) or knockdown (in CD157-positive cells) affected cell growth, migration, invasion and tumorigenicity, most notably in biphasic MPM cell lines. In these cells, CD157 expression was associated with increased activation of the mTOR signaling pathway, resulting in decreased platinum sensitivity. Moreover, a trend towards reduced survival was observed in patients with biphasic MPM receiving postoperative platinum-based chemotherapy. These findings indicate that CD157 is implicated in multiple aspects of MPM progression and suggest that CD157 expression could be used to stratify patients into different prognostic groups or to select patients that might benefit from particular chemotherapeutic approach.
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy; These authors equally contributed to this work.
authors.forename: Erika
authors.initials: E
authors.lastname: Ortolan
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy; These authors equally contributed to this work.
authors.forename: Alice
authors.initials: A
authors.lastname: Giacomino
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Martinetto
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Morone
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lo Buono
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Ferrero
authors.affiliation: Department of Oncology, University of Torino, San Luigi Hospital, Orbassano, Italy; Interdepartmental Center "G. Scansetti" for Studies on Asbestos and other Toxic Particulates, University of Torino, Torino, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.affiliation: Department of Oncology, University of Torino, San Luigi Hospital, Orbassano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Pathology Unit, Azienda Ospedaliera Nazionale SS, Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Orecchia
authors.affiliation: Department of Surgery, Section of Thoracic Surgery, University of Torino, Torino, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.affiliation: Department of Oncology, University of Torino, San Luigi Hospital, Orbassano, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Rapa
authors.affiliation: Department of Oncology, University of Torino, San Luigi Hospital, Orbassano, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.affiliation: Department of Oncology, University of Torino, San Luigi Hospital, Orbassano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino, Italy; Interdepartmental Center "G. Scansetti" for Studies on Asbestos and other Toxic Particulates, University of Torino, Torino, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Funaro
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000032:analysis / Q000096:biosynthesis*; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2