A pan-cancer analysis of the clinical and genetic portraits of somatostatin receptor expressing tumor as a potential target of peptide ... View Full Text


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Article Info

DATE

2020-04-25

AUTHORS

Hyunjong Lee, Minseok Suh, Hongyoon Choi, Seunggyun Ha, Jin Chul Paeng, Gi Jeong Cheon, Keon Wook Kang, Dong Soo Lee

ABSTRACT

PurposeAlthough 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.MethodsSST 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.ResultsWe 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.ConclusionA 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. More... »

PAGES

42

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    21 schema:description PurposeAlthough 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.MethodsSST 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.ResultsWe 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.ConclusionA 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.
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    27 schema:keywords Cancer Genome Atlas
    28 Cox proportional regression analysis
    29 Genome Atlas
    30 IDH1 mutation
    31 LGG patients
    32 PCPG
    33 ResultsWe
    34 alterations
    35 analysis
    36 applications
    37 aspects
    38 association
    39 atlas
    40 base
    41 better prognosis
    42 better understanding
    43 breast cancer subjects
    44 breast invasive carcinoma
    45 broad range
    46 cancer
    47 cancer subjects
    48 cancer subtypes
    49 cancer types
    50 carcinoma
    51 clinical application
    52 clinical aspects
    53 clinicopathologic features
    54 correlation analysis
    55 current clinical applications
    56 data
    57 diverse cancer subtypes
    58 expression
    59 expression levels
    60 expression patterns
    61 features
    62 findings
    63 gastroenteropancreatic neuroendocrine tumors
    64 genetic features
    65 genetic portrait
    66 genomic alterations
    67 gliomas
    68 grade
    69 higher proportion
    70 histology
    71 hormone receptor status
    72 imaging
    73 indications
    74 interactive tool
    75 invasive carcinoma
    76 knowledge base
    77 landscape
    78 levels
    79 low-grade gliomas
    80 major target
    81 mutations
    82 neuroendocrine tumors
    83 organs
    84 pan-cancer analysis
    85 patients
    86 patterns
    87 peptide receptor imaging
    88 peptide receptor radiotherapy
    89 pheochromocytoma
    90 poor prognosis
    91 portrait
    92 potential target
    93 profile
    94 prognosis
    95 prognostic value
    96 promising theranostic target
    97 proportion
    98 proportional regression analysis
    99 radiotherapy
    100 range
    101 receptor imaging
    102 receptor radiotherapy
    103 receptor status
    104 receptors
    105 regression analysis
    106 resources
    107 results
    108 sST2 levels
    109 samples
    110 scope
    111 significant association
    112 somatostatin receptors
    113 sst subtype 2
    114 sst-expressing tumors
    115 sst2 expression
    116 status
    117 subjects
    118 subtype 2
    119 subtypes
    120 target
    121 theranostic target
    122 therapy
    123 threshold
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    126 tumor grade
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