Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry

Janos Schmidt, Béla Kajtár, Kata Juhász, Mária Péter, Tamás Járai, András Burián, L. Kereskai, Imre Gerlinger, Tamás Tornóczki, Gábor Balogh, L. Vígh, Lászó Márk, Zsolt Balogi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2702-2717
Number of pages16
JournalOncotarget
Volume11
Issue number28
DOIs
Publication statusPublished - Jul 14 2020

Keywords

  • Imaging mass spectrometry
  • Lipid tumor marker
  • S100A8
  • S100A9
  • Tumor marker

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry'. Together they form a unique fingerprint.

  • Cite this

    Schmidt, J., Kajtár, B., Juhász, K., Péter, M., Járai, T., Burián, A., Kereskai, L., Gerlinger, I., Tornóczki, T., Balogh, G., Vígh, L., Márk, L., & Balogi, Z. (2020). Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry. Oncotarget, 11(28), 2702-2717. https://doi.org/10.18632/oncotarget.27649