Expression profiling on subclasses of primary parotid gland carcinomas

Jeannine Meinrath; Anja Haak; Nesrin Igci; Priya Dalvi; Christoph Arolt; Sonja Meemboor; Udo Siebolts; Hannah Eischeidt-Scholz; Claudia Wickenhauser; Inga Grünewald; Uta Drebber; Reinhard Büttner; Alexander Quaas; Jens-Peter Klußmann; Margarete Odenthal; Dirk Beutner; Moritz Meyer

doi:10.18632/oncotarget.27797

Expression profiling on subclasses of primary parotid gland carcinomas

Oncotarget. 2020 Nov 10;11(45):4123-4137. doi: 10.18632/oncotarget.27797.

Authors

Jeannine Meinrath¹, Anja Haak², Nesrin Igci¹, Priya Dalvi^{1

3}, Christoph Arolt¹, Sonja Meemboor^{1

4}, Udo Siebolts², Hannah Eischeidt-Scholz¹, Claudia Wickenhauser², Inga Grünewald⁵, Uta Drebber^{1

4}, Reinhard Büttner^{1

3

4}, Alexander Quaas^{1

4}, Jens-Peter Klußmann^{4

6}, Margarete Odenthal^{1

3

4}, Dirk Beutner^{6

7}, Moritz Meyer^{6

8}

Affiliations

¹ Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
² Department of Pathology, University of Halle, Halle, Germany.
³ Center for Molecular Medicine, University of Cologne, Cologne, Germany.
⁴ Center of Integrative Oncology, University Hospital of Cologne, Cologne, Germany.
⁵ Department of Pathology, University Hospital of Münster, Münster, Germany.
⁶ Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany.
⁷ Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Göttingen, Göttingen, Germany.
⁸ Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany.

Abstract

Introduction: The underlying molecular mechanisms of parotid gland carcinomas (PGC) are still unknown. Knowledge about the tumor-driving signaling pathways is necessary either for diagnostics or developing new therapeutic options in this heterogeneous and rare entity.

Material and methods: 94 matching RNA formalin-fixed and paraffin-embedded tissue samples from PGC and the corresponding non-tumor area, RNA quality and quantity were sufficient for gene expression profiling of 770 genes using the NanoString's nCounter technology. Oncogenic and tumor suppressor genes were examined in the three common PGC tumor entities: adenoid cystic carcinoma (ACC), adenocarcinoma NOS (AC-NOS), and mucoepidermoid carcinoma (MEC).

Results: Expression profiling and subsequent hierarchical cluster analysis clearly differentiated between non-tumor gland tissue samples and PGC. In addition expression pattern of all three entities differed. The extensive pathway analysis proved a prominent dysregulation of the Wnt signaling pathway in the three PGC entities. Moreover, transcript upstream analysis demonstrated a pronounced activation of the PI3K pathway in ACC and MEC.

Discussion: Our findings revealed divergent molecular expression profiles in MEC, ACC and AC-NOS that are presently studied for their potential application in PGC diagnostics. Importantly, identification of Wnt and PI3K signaling in PGC revealed novel options of PGC therapy.

Keywords: cancer; gene expression; nanostring; pancancer pathway; salivary gland.