Amy Dickinson1, Mayank Saraswat2, Antti Mäkitie3, Robert Silén4, Jaana Hagström5, Caj Haglund6, Sakari Joenväärä7, Suvi Silén8. 1. Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Finland; Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address: Amy.dickinson@helsinki.fi. 2. Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Finland; HUSLAB, Helsinki University Hospital, Helsinki 00290, Finland. Electronic address: sarawat.mk@gmail.com. 3. Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Electronic address: antti.makitie@helsinki.fi. 4. Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Finland. Electronic address: robert.silen@iki.fi. 5. HUSLAB, Helsinki University Hospital, Helsinki 00290, Finland; Department of Pathology, University of Helsinki, Finland. Electronic address: jaana.hagstrom@hus.fi. 6. Department of Surgery, University of Helsinki and Helsinki, University Hospital, Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland. Electronic address: caj.haglund@helsinki.fi. 7. Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Finland; HUSLAB, Helsinki University Hospital, Helsinki 00290, Finland. Electronic address: sakari.joenvaara@helsinki.fi. 8. Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. Electronic address: suvi.silen@helsinki.fi.
Abstract
OBJECTIVES: No prognostic or predictive biomarkers for oral squamous cell carcinoma (OSCC) exist. We aimed to discover novel proteins, altered in OSCC, to be further investigated as potential biomarkers, and to improve understanding about pathways involved in OSCC. MATERIALS AND METHODS: Proteomic signatures of seven paired healthy and OSCC tissue samples were identified using ultra-definition quantitative mass spectrometry, then analysed and compared using Anova, principal component analysis, hierarchical clustering and OPLS-DA modelling. A selection of significant proteins that were also altered in the serum from a previous study (PMID: 28632724) were validated immunohistochemically on an independent cohort (n = 66) to confirm immunopositivity and location within tumour tissue. Ingenuity Pathways Analysis was employed to identify altered pathways. RESULTS: Of 829 proteins quantified, 257 were significant and 72 were able to classify healthy vs OSCC using OPLS-DA modelling. We identified 19 proteins not previously known to be upregulated in OSCC, including prosaposin and alpha-taxilin. KIAA1217 and NDRG1 were upregulated in stage IVa compared with stage I tumours. Altered pathways included calcium signalling, cellular movement, haematological system development and function, and immune cell trafficking, and involved NF-kB and MAPK networks. CONCLUSIONS: We found a set of proteins reliably separating OSCC tumour from healthy tissue, and multiple proteins differing between stage I and stage IVa OSCC. These potential biomarkers can be studied and validated in larger cohorts.
OBJECTIVES: No prognostic or predictive biomarkers for oral squamous cell carcinoma (OSCC) exist. We aimed to discover novel proteins, altered in OSCC, to be further investigated as potential biomarkers, and to improve understanding about pathways involved in OSCC. MATERIALS AND METHODS: Proteomic signatures of seven paired healthy and OSCC tissue samples were identified using ultra-definition quantitative mass spectrometry, then analysed and compared using Anova, principal component analysis, hierarchical clustering and OPLS-DA modelling. A selection of significant proteins that were also altered in the serum from a previous study (PMID: 28632724) were validated immunohistochemically on an independent cohort (n = 66) to confirm immunopositivity and location within tumour tissue. Ingenuity Pathways Analysis was employed to identify altered pathways. RESULTS: Of 829 proteins quantified, 257 were significant and 72 were able to classify healthy vs OSCC using OPLS-DA modelling. We identified 19 proteins not previously known to be upregulated in OSCC, including prosaposin and alpha-taxilin. KIAA1217 and NDRG1 were upregulated in stage IVa compared with stage I tumours. Altered pathways included calcium signalling, cellular movement, haematological system development and function, and immune cell trafficking, and involved NF-kB and MAPK networks. CONCLUSIONS: We found a set of proteins reliably separating OSCC tumour from healthy tissue, and multiple proteins differing between stage I and stage IVa OSCC. These potential biomarkers can be studied and validated in larger cohorts.