Characterization of Somatostatin Receptor 2 Gene Expression and Immune Landscape in Sinonasal Malignancies

Elisabetta Xue, Dara Bracken-Clarke, Harris Krause, Tolulope Adeyelu, Mark G. Evans, Dilara Akbulut, Martha Quezado, Nishant Gandhi, Alex Farrell, Heloisa P. Soares, Emil Lou, Minh Phan, Rusha Patel, Ari M. Vanderwalde, Andrew Elliott, Conor E. Steuer, Nabil F. Saba, Daniel J. Lubin, Nyall R. London, James L. GulleyCharalampos S. Floudas

Research output: Contribution to journalArticlepeer-review

Abstract

Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene (SSTR2), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzed SSTR2 gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database. SSTR2 gene expression was high in neural-type ONB and low in basal-type ONB and in most of the SNUC and SNEC cases; there was no difference in expression between primary and metastatic tumors. The T cell-inflamed (TCI) score analysis classified 38.5% of SNUC cases as T cell-inflamed compared to only 3.9% of ONB and 0% of SNEC cases; 26.9% of ONB cases were classified as intermediate TCI; and SNEC had the lowest relative immune cell infiltration by deconvolution. In high SSTR2-expressing ONB, there was a higher proportion of infiltrating of Natural Killer cells and dendritic cells by deconvolution. Additionally, high SSTR2-expressing ONB was enriched for proliferation pathways, including E2F and Myc targets and G2M checkpoints. In conclusion, our findings delineate significant differences between these three types of sinonasal malignancies that were examined. In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.

Original languageEnglish (US)
Article number3931
JournalCancers
Volume16
Issue number23
DOIs
StatePublished - Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • exome sequencing
  • olfactory neuroblastoma
  • RNA-Seq
  • sinonasal neuroendocrine carcinoma
  • sinonasal undifferentiated carcinoma
  • somatostatin receptor 2
  • tumor biomarkers
  • tumor microenvironment

PubMed: MeSH publication types

  • Journal Article

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