The Molecular and Immunological Landscape in Nasopharyngeal Carcinoma (NPC) Differs by Somatostatin Receptor 2 (SSTR2) Expression.

Somatostatin receptor 2 is expressed in nasopharyngeal carcinoma (NPC). We report genomic and transcriptomic analysis results of 163 NPC cases, demonstrating that somatostatin receptor 2 (SSTR2) gene expression in EBV-positive and in EBV-negative NPC correlated with genomic alterations and an inflamed microenvironment. Median SSTR2 expression was 6.52 transcripts per million (TPM), ranging from 0.59 TPM (Quartile 1 [Q1], 18.2% EBV-positive) to 35.79 TPM (Q4, 82.9% EBV-positive). PIK3CA (20.51%) and CYLD (10.53%)/NFKBIA (12.82%) mutations were enriched in SSTR2-Q1 versus -Q4. Tumor mutation burden was negatively correlated (R = -0.27, p < 0.001) with SSTR2, while PD-L1 tumor proportion score (2% vs. 92.5% [SSTR2:Q1 vs. Q4], p < 0.001) and T-cell inflamed score correlated with SSTR2 expression (R = 0.53, p < 0.001). B-cells, M1 macrophages, CD8+ T-cells, Treg cells, and dendritic cells were enriched in SSTR2-Q4, while neutrophils were prominent in SSTR2-Q1. These results demonstrate a significant positive correlation between SSTR2 expression and an inflamed tumor microenvironment in NPC. This suggests that SSTR2 expression in NPC may be a clinically useful biomarker, correlating with the tumor microenvironment (including, potentially, sensitivity to immunotherapy) and its genetic profile.