TY - JOUR
T1 - Characterization of Somatostatin Receptor 2 Gene Expression and Immune Landscape in Sinonasal Malignancies
AU - Xue, Elisabetta
AU - Bracken-Clarke, Dara
AU - Krause, Harris
AU - Adeyelu, Tolulope
AU - Evans, Mark G.
AU - Akbulut, Dilara
AU - Quezado, Martha
AU - Gandhi, Nishant
AU - Farrell, Alex
AU - Soares, Heloisa P.
AU - Lou, Emil
AU - Phan, Minh
AU - Patel, Rusha
AU - Vanderwalde, Ari M.
AU - Elliott, Andrew
AU - Steuer, Conor E.
AU - Saba, Nabil F.
AU - Lubin, Daniel J.
AU - London, Nyall R.
AU - Gulley, James L.
AU - Floudas, Charalampos S.
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - exome sequencing
KW - olfactory neuroblastoma
KW - RNA-Seq
KW - sinonasal neuroendocrine carcinoma
KW - sinonasal undifferentiated carcinoma
KW - somatostatin receptor 2
KW - tumor biomarkers
KW - tumor microenvironment
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U2 - 10.3390/cancers16233931
DO - 10.3390/cancers16233931
M3 - Article
C2 - 39682120
AN - SCOPUS:85212147456
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 23
M1 - 3931
ER -