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Abstract
PURPOSE:
Although somatostatin receptor (SST) is a promising theranostic target and is widely expressed in tumors of various organs, the indication for therapies targeting SST is limited to typical gastroenteropancreatic neuroendocrine tumors (NETs). Thus, broadening the scope of the current clinical application of peptide receptor radiotherapy (PRRT) can be supported by a better understanding of the landscape of SST-expressing tumors.

METHODS:
SST expression levels were assessed in data from The Cancer Genome Atlas across 10,701 subjects representing 32 cancer types. As the major target of PRRT is SST subtype 2 (SST2), correlation analyses between the pan-cancer profiles, including clinical and genetic features, and SST2 level were conducted. The median SST2 expression level of pheochromocytoma and paraganglioma (PCPG) samples was used as the threshold to define "high-SST2 tumors." The prognostic value of SST2 in each cancer subtype was evaluated by using Cox proportional regression analysis.

RESULTS:
We constructed a resource of SST expression patterns associated with clinicopathologic features and genomic alterations. It provides an interactive tool to analyze SST expression patterns in various cancer types. As a result, eight of the 31 cancer subtypes other than PCPG had more than 5% of tumors with high-SST2 expression. Low-grade glioma (LGG) showed the highest proportion of high-SST2 tumors, followed by breast invasive carcinoma (BRCA). LGG showed different SST2 levels according to tumor grade and histology. IDH1 mutation was significantly associated with high-SST2 status. In BRCA, the SST2 level was different according to the hormone receptor status. High-SST2 status was significantly associated with good prognosis in LGG patients. High-SST2 status showed a trend for association with poor prognosis in triple-negative breast cancer subjects.

CONCLUSION:
A broad range of SST2 expression was observed across diverse cancer subtypes. The SST2 expression level showed a significant association with genomic and clinical aspects across cancers, especially in LGG and BRCA. These findings extend our knowledge base to diversify the indications for PRRT as well as SST imaging.

Author information

Lee H1,2, Suh M1,2, Choi H3, Ha S4, Paeng JC1, Cheon GJ1,5, Kang KW1,5, Lee DS1,2.
1
Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-Gu, Seoul, 110-744, Republic of Korea.
2
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
3
Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-Gu, Seoul, 110-744, Republic of Korea. chy1000@snu.ac.kr.
4
Division of Nuclear Medicine, Department of Radiology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
5
Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.