Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry
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Janos Schmidt1, Béla Kajtár2, Kata Juhász1, Mária Péter3, Tamás Járai4, András Burián4, László Kereskai2, Imre Gerlinger4, Tamás Tornóczki2, Gábor Balogh3, László Vígh3, Lászó Márk1,5,6,* and Zsolt Balogi1,*
1 Institute of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Pécs, Hungary
2 Department of Pathology, Medical School, University of Pécs, Pécs, Hungary
3 Institute of Biochemistry, Biological Research Center, Szeged, Hungary
4 Department of Oto-Rhino-Laryngology, Medical School, University of Pécs, Pécs, Hungary
5 MTA-PTE Human Reproduction Group, Medical School, University of Pécs, Pécs, Hungary
6 Imaging Center for Life and Material Sciences, Medical School, University of Pécs, Pécs, Hungary
* These authors contributed equally to this work
Keywords: Imaging mass spectrometry; tumor marker; lipid tumor marker; S100A8; S100A9
Received: November 30, 2019 Accepted: June 01, 2020 Published: July 14, 2020
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To improve pre- and post-operative diagnosis and prognosis novel molecular markers are desirable. Here we used MALDI imaging mass spectrometry (IMS) and immunohistochemistry (IHC) to seek tumor specific expression of proteins and lipids in HNSCC samples. Among low molecular weight proteins visualized, S100A8 and S100A9 were found to be expressed in the regions of tumor tissue but not in the surrounding healthy stroma of a post-operative microdissected tissue. Marker potential of S100A8 and S100A9 was confirmed by immunohistochemistry of paraffin-embedded pathological samples. Imaging lipids showed a remarkable depletion of lysophosphatidylcholine species LPC[16:0], LPC[18:2] and, in parallel, accumulation of major glycerophospholipid species PE-P[36:4], PC[32:1], PC[34:1] in neoplastic areas. This was confirmed by shotgun lipidomics of dissected healthy and tumor tissue sections. A combination of the negative (LPC[16:0]) and positive (PC[32:1], PC[34:1]) markers was also applicable to uncover tumorous character of a pre-operative biopsy. Furthermore, marker potential of lysophospholipids was supported by elevated expression levels of the lysophospholipid degrading enzyme lysophospholipase A1 (LYPLA1) in the tumor regions of paraffin-embedded HNSCC samples. Finally, experimental evidence of 3D cell spheroid tests showed that LPC[16:0] facilitates HNSCC invasion, implying that HNSCC progression in vivo may be dependent on lysophospholipid supply. Altogether, a series of novel proteins and lipid species were identified by IMS and IHC screening, which may serve as potential molecular markers for tumor diagnosis, prognosis, and may pave the way to better understand HNSCC pathophyisiology.
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