Gastric inhibitory polypeptide receptor (GIPR) is a promising target for imaging and therapy in neuroendocrine tumors
Gastric inhibitory polypeptide receptor (GIPR) is a promising target for imaging and therapy in neuroendocrine tumors
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DOI：
10.1016/j.surg.2013.04.052
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发表时间：
2013-12-01
期刊：
影响因子：
3.8
通讯作者：
Howe, James R.
中科院分区：
文献类型：
--
作者：
Sherman, Scott K.;Carr, Jennifer C.;Howe, James R.
背景结合生长抑素受体2型（SSTR 2）的配体可用于神经内分泌肿瘤（NET）的成像和治疗，但并非所有肿瘤都表达高水平的这些受体。本研究的目的是评估相对于SSTR 2的NETs中新治疗靶点的基因表达。从103例原发性小肠和胰腺NET、匹配的正常组织和123例转移瘤中提取RNA。采用定量聚合酶链反应（PCR）检测12个候选基因的表达，并与SSTR 2进行比较。相对于正常组织，SSTR 2、GPR98、BRS 3、GIPR、GRM 1和OPRK 1的原代NET表达分别增加3、8、13、13、17和20倍。在转移瘤中也发现了类似的变化。虽然大多数候选基因的绝对表达量低于SSTR 2，但绝对表达量。GIPR表达最接近SSTR 2（平均dCT 3.6 vs 2.7，P = .01）。OPRK1和OXTR的绝对表达在不同的原发肿瘤类型中差异很大，在小肠NETs中与SSTR 2接近，而在胰腺NETs中则不一样。与目前的治疗标准SSTR 2相比，GIPR在肿瘤组织中的绝对基因表达量仅略低，但在正常组织中的表达量低得多，使其成为NET成像和治疗的有希望的新靶点。
Background. Ligands binding the somatostatin receptor type 2 (SSTR2) are useful for imaging and treatment of neuroendocrine tumors (NETs), but not all tumors express high levels of these receptors. The aim of this study was to evaluate gene expression of new therapeutic targets in NETs relative to SSTR2.Methods. RNA was extracted from 103 primary small bowel and pancreatic NETs, matched normal tissue, and 123 metastases. Expression of 12 candidate genes was measured by quantitative polymerase chain reaction normalized to internal controls; candidate gene expression was compared with SSTR2.Results. Relative to normal tissue, primary NET expression of SSTR2, GPR98, BRS3, GIPR, GRM1, and OPRK1 were increased by 3, 8, 13, 13, 17, and 20-fold, respectively. Similar changes were found in metastases. Although most candidate genes showed lesser absolute expressions than SSTR2, absolute. GIPR expression was closest to SSTR2 (mean dCT 3.6 vs 2.7, P = .01). Absolute OPRK1 and OXTR expression varied greatly by primary tumor type and was close to SSTR2 in small bowel NETs but not pancreatic NETs.Conclusion. Compared with the current treatment standard SSTR2, GIPR has only somewhat lesser absolute gene expression in tumor tissue but much lesser expression in normal tissue, making it promising new target for NET imaging and therapy.