Somatostatin receptors in gastrointestinal stromal tumors: new prognostic biomarker and potential therapeutic strategy

胃肠道间质瘤中的生长抑素受体:新的预后生物标志物和潜在治疗策略

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作者:Wen-Yi Zhao,Chun Zhuang,Jia Xu,Ming Wang,Zi-Zhen Zhang,Lin Tu,Chao-Jie Wang,Tian-Long Ling,Hui Cao,Zhi-Gang Zhang

Abstract

Somatostatin receptors (SSTRs) already act as important roles in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with high expression levels for prognosis predicting and octreotide LAR treatment purposes but less noticed in gastrointestinal stromal tumors (GISTs). Our study aims to fully evaluate the expression levels and prognostic values of SSTRs in GIST patients. For SSTRs expression detection, qPCR were used in 25 fresh GIST specimens, and then, 453 GIST samples (405 GISTs with operation only and 48 with imatinib adjuvant therapy after surgery) were collected for tissue microarrays (TMAs) construction and confirmed by immunohistochemistry (IHC). Clinicopathological data were confirmed by pathological diagnosis and clinical recorders, recurrence-free survivals (RFS) were evaluated in 453 GIST patients. With IHC performed, SSTR1 and SSTR2 present high positive proportion (81.9% and 87.6%) in 453 GISTs in our study, and positive expression rates of SSTR3, SSTR4 and SSTR5 are 56.1%, 8.8% and 47.2%, respectively. SSTR2 and SSTR5 negative expression are associated with decreased RFS when compared to positive cases by Kaplan-Meier survival analyses with log-rank test and univariate analysis in GISTs, furthermore, SSTR2 was an independent prognostic indicator for GISTs by multivariate analysis. In our study, detection of SSRT2 and SSTR5 expression helps to predict different prognosis in GIST patients. SSTR2 is a novel independent prognostic biomarker for GISTs. With high expression performance of SSTRs in GISTs, new therapeutic strategies such as octreotide or pasireotide LAR could be taken into consideration in selected advanced GIST patients.

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