AUTHOR=Wang Aoyun , Yuan Yixiao , Chu Han , Gao Yixing , Jin Zheng , Jia Qingzhu , Zhu Bo 

TITLE=Somatostatin Receptor 2: A Potential Predictive Biomarker for Immune Checkpoint Inhibitor Treatment

JOURNAL=Pathology and Oncology Research

VOLUME=28

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610196

DOI=10.3389/pore.2022.1610196

ISSN=1532-2807

ABSTRACT=<p>Somatostatin receptor 2 (<italic>SSTR2</italic>), the most abundant receptor of somatostatin (<italic>SST</italic>), possesses immunoreactivity and is altered in many cancers. However, the association between <italic>SSTR2</italic> and efficacy of immune checkpoint inhibitors (ICIs) has not yet been reported. Immunohistochemistry (IHC) information across 20 cancers was collected from the Human Protein Atlas (HPA) and used to analyze the expression of <italic>SSTR2</italic>. Immune signatures collected from public databases, such as BioCarta or Reactome, were used to investigate the association between <italic>SSTR2</italic> and the tumor microenviroment in the Cancer Genome Atlas (TCGA). Data from cohorts treated with ICIs were collected to assess whether <italic>SSTR2</italic> is associated with benefits from ICIs treatment. In the HPA, we found the <italic>SSTR2</italic> IHC-positive rate of 13 cancers to be above 50%. Five types of cancer express <italic>SSTR2</italic> mildly (positive rate: 25%–50%), while the remaining two types of cancer barely stained <italic>SSTR2</italic>-positive (positive rate: 0%–24%). In TCGA analysis, immune cell signatures and immune function pathways were enriched in high <italic>SSTR2</italic> expression groups in most cancers. In each ICIs treated cohort, patients with high <italic>SSTR2</italic> expression experienced numerically superior objective response rate (Braun: 14.8% vs 13.4%, <italic>p</italic> = 0.85; Gide: 69.4% vs 40.5%, <italic>p</italic> = 0.025; Mariathasan: 22.4% vs 16.7%, <italic>p</italic> = 0.233; Miao: 37.5% vs 11.8%; Riaz: 32.0% vs 7.7%, <italic>p</italic> = 0.067) and overall survival (Braun: HR (95%CI): 0.80 [0.62–1.04], <italic>p</italic> = 0.80; Gide: HR (95%CI): 0.61 [0.29–1.30], <italic>p</italic> = 0.20; Mariathasan: HR (95%CI): 0.83 [0.64–1.08], <italic>p</italic> = 0.16; Miao: HR (95%CI): 0.24 [0.086–0.65], <italic>p</italic> = 0.0028; Nathanson cohort: HR (95%CI): 0 [0-inf], <italic>p</italic> = 0.18; Riaz: HR (95%CI): 0.24 [0.086–0.65], <italic>p</italic> = 0.028) than patients with low <italic>SSTR2</italic> expression. In pooled cohort, we found these differences were significant (Pool: 24.6% vs 16.7%, <italic>p</italic> = 0.0077; HR (95% CI): 0.77 [0.65–0.91], <italic>p</italic> = 0.0018). Our results suggest that <italic>SSTR2</italic> is a potential predictive biomarker for response to ICIs.</p>