PTEN公司
PI3K/AKT/mTOR通路
癌症研究
生长抑素受体
分级(工程)
转移
神经内分泌肿瘤
生长抑素
原发性肿瘤
生长抑素受体2
生物
肿瘤科
内科学
医学
信号转导
癌症
细胞生物学
生态学
作者
Chiara Borga,Carlo Alberto Dal Pozzo,Elisabetta Trevellin,Francesca Bergamo,Sabina Murgioni,Anna Caterina Milanetto,Claudio Pasquali,Umberto Cillo,Giada Munari,Chiara Martini,Eugenio De Carlo,Vittorina Zagonel,Vincenza Guzzardo,Gianmaria Pennelli,Matteo Fassan,Roberto Vettor
出处
期刊:Endocrine-related Cancer
[Bioscientifica]
日期:2021-07-01
卷期号:28 (7): 449-456
被引量:2
摘要
The knowledge of the molecular landscape of ileal neuroendocrine tumors (NETs) is affected by the lack of systematic studies investigating intra-tumoral heterogeneity. In this study, intra-tumoral heterogeneity was investigated in 27 primary ileal G1-NETs and their matched nodal and liver metastases in order to assess the tumor grading, the expression status of two somatostatin receptor isoforms (i.e. SSTR2A and SSTR5) and mTOR signaling dysregulation (ph-mTOR, ph-p70S6K, ph-4EBP1, PTEN and miR-21). Among the 27 G1 primary tumors, 4 shifted to G2 in the matched liver metastasis. Although mTOR activation was pretty consistent between primary and secondary malignancies, mTOR effectors (ph-p70S6K and ph-4EBP1) were overexpressed in matched liver metastases, whereas PTEN expression profile changed in only two cases. MiR-21 was significantly up-regulated in the metastatic setting. Although SSTRs expression was present in most of the primary tumors and matched metastasis, we found SSTR5 expression to be significantly increased in liver metastases. Notably, SSTRs expression was heterogeneous within the same lesions in most of the lesions. Overall, despite primary and metastatic ileal NETs show a similar molecular landscape, tumor grading and mTOR signaling pathway may diverge in the metastatic setting, thus affecting prognosis and treatment.
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