title: Lumican is overexpressed in lung adenocarcinoma pleural effusions.
abstract: Adenocarcinoma (AdC) is the most common lung cancer subtype and is often associated with pleural effusion (PE). Its poor prognosis is attributable to diagnostic delay and lack of effective treatments and there is a pressing need in discovering new biomarkers for early diagnosis or targeted therapies. To date, little is known about lung AdC proteome. We investigated protein expression of lung AdC in PE using the isobaric Tags for Relative and Absolute Quantification (iTRAQ) approach to identify possible novel diagnostic/prognostic biomarkers. This provided the identification of 109 of lung AdC-related proteins. We further analyzed lumican, one of the overexpressed proteins, in 88 resected lung AdCs and in 23 malignant PE cell-blocks (13 lung AdCs and 10 non-lung cancers) using immunohistochemistry. In AdC surgical samples, lumican expression was low in cancer cells, whereas it was strong and diffuse in the stroma surrounding the tumor. However, lumican expression was not associated with tumor grade, stage, and vascular/pleural invasion. None of the lung cancer cell-blocks showed lumican immunoreaction, whereas those of all the other tumors were strongly positive. Finally, immunoblotting analysis showed lumican expression in both cell lysate and conditioned medium of a fibroblast culture but not in those of A549 lung cancer cell line. PE is a valid source of information for proteomic analysis without many of the restrictions of plasma. The high lumican levels characterizing AdC PEs are probably due to its release by the fibroblasts surrounding the tumor. Despite the role of lumican in lung AdC is still elusive, it could be of diagnostic value.
authors.affiliation: Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cappellesso
authors.affiliation: Department of Medicine and Proteomics Center, University of Padua; Padua, PD, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Millioni
authors.affiliation: Department of Biomedical Sciences, University of Padua and Proteomics Center of Padua University, Padua, PD, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arrigoni
authors.affiliation: Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonato
authors.affiliation: Department of Medicine, Internal Medicine 4, University of Padua, Padua, PD, Italy.
authors.forename: Brasilina
authors.initials: B
authors.lastname: Caroccia
authors.affiliation: Department of Medicine, Metabolism Division, University of Padua, Padua, PD, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.affiliation: Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.affiliation: Department of Statistical Sciences, University of Padua, Padua, PD, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ventura
authors.affiliation: Department of Medicine, Metabolism Division, University of Padua, Padua, PD, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tessari
authors.affiliation: Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy.
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007632:Keratan Sulfate / Q000378:metabolism*; D000071234:Lumican; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016066:Pleural Effusion, Malignant / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; D000071234:Lumican; D020543:Proteome; D007632:Keratan Sulfate