A pan-cancer analysis of the clinical and genetic portraits of somatostatin receptor expressing tumor

Introduction: Somatostatin receptor (SSTR) targeting peptide receptor radiotherapy (PRRT) has been successfully introduced to the clinic, treating well-differentiated neuroendocrine tumor (NET) patients. Although SSTR is a promising theranostics target, the indication is limited to typical NET. Thus, broadening the scope of current clinical application is necessary. Here, we analyzed the clinical and genetic portraits related to SSTR expression across 9962 subjects representing 32 cancers.

Methods: SSTR expression levels were assessed by RNA-seq data of the Cancer Genome Atlas. As the major target of PRRT is SSTR subtype 2 (SSTR2), correlation analyses between the pan-cancer profiles, including clinical and genetic features, and SSTR2 level were conducted. Median SSTR2 expression level of Pheochromocytoma and Paraganglioma (PCPG) samples was used as threshold to define ’high-SSTR2 tumor’. Prognostic value of SSTR2 in each cancer subtypes was evaluated by using Cox proportional regression analysis.

Results: Firstly, eight of the 31 cancer subtypes except PCPG had more than 5% of high-SSTR2 tumors and 20 of them had more than 1% of high-SSTR2 tumors. Low grade glioma (LGG) showed the highest ratio (50.2%) of high-SSTR tumors, followed by breast invasive carcinoma (BRCA) (16.1%). The significant correlation between pan-cancer profile and SSTR expression was observed. Overall, high SSTR2 level was associated with good prognosis. Specifically, LGG showed different SSTR2 level according to the tumor grade and histology. IDH1 mutation was significantly associated with high-SSTR2 status. In BRCA, SSTR2 level was different according to the hormone receptor status. Survival analysis revealed that high-SSTR2 status were significantly associated with good prognosis in LGG (p < 0.001) and pancreatic ductal adenocarcinoma (p = 0.014) subjects. No significant prognostic impact was shown in whole breast cancer subjects, however, high-SSTR2 status reflected poor prognosis (p = 0.034) when limited to triple negative breast cancer subjects.

Conclusions: Broad range of SSTR2 expression was observed across the diverse cancer subjects. The integrated genetic and clinical analyses of pan-cancer profile according to SSTR status extends our knowledge base to diversify the theranostics indication for PRRT.