title: Proteomic profiling identifies the inorganic pyrophosphatase (PPA1) protein as a potential biomarker of metastasis in laryngeal squamous cell carcinoma.
abstract: Relapse and metastasis are the main causes of unfavorable outcome in head and neck cancers. Whereas, understanding of the molecular background of these processes is far from being complete. Therefore, in this study we aimed to identify potential biomarker candidates of relapse and metastasis in laryngeal squamous cell carcinoma (LSCC) by combining the 2D electrophoresis based protein screen and immunohistochemical analysis of candidate proteins. We screened three groups of LSCC cell lines derived from primary tumors, recurrent tumors and metastases and identified seven proteins that differed significantly in relative abundance between the analyzed groups. Among the identified proteins were the heat shock proteins HSP60 and HSP70 that were significantly downregulated both in recurrences- and metastases-derived cell lines but not in primary tumor-derived cell lines. Moreover, we identified significant upregulation of the annexin V, calreticulin and the inorganic pyrophosphatase (PPA1) exclusively in the metastases-derived cell lines. As these upregulated proteins could potentially become novel biomarkers of metastasis, we have compared their abundance in primary tumor LSCC N(0) cases, primary tumor LSCC N(+) cases as well as in LSCC metastases N(+). Our results show an intense increase of cytoplasmic PPA1 abundance in the N(+) (p = 0.000042) compared to the N(0) group. In summary, we show a group of proteins deregulated in recurrences and metastases of LSCC. Moreover, we suggest the PPA1 protein as a potential new biomarker for metastasis in this cancer.
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bodnar
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.|Institute of Chemical Technology and Engineering, Poznan University of Technology, Poznan, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Luczak
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Bednarek
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szylberg
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.|Chair of Oncologic Pathology and Epidemiology, Poznan University of Medical Sciences and Greater Poland Cancer Center, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszalek
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Turku University Hospital and University of Turku, Turku, Finland.|Department of Medical Biochemistry, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Reidar
authors.initials: R
authors.lastname: Grenman
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.|Department of Audiology and Phoniatrics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szyfter
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.|Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jarmuz-Szymczak
authors.affiliation: Department of Cancer Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. giefingm@man.poznan.pl.|Department of Otolaryngology and Laryngeal Oncology, Poznan University of Medical Sciences, Poznan, Poland. giefingm@man.poznan.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Giefing
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D043564:Inorganic Pyrophosphatase / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D040901:Proteomics
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D043564:Inorganic Pyrophosphatase
keywords: Biomarker; LSCC; Laryngeal cancer; Metastasis; PPA1