Analysis of the genetic and molecular pathogenesis in enteropancreatic neuroendocrine tumors

肠胰腺神经内分泌肿瘤由多种罕见病变组成，根据其产生的激素命名。虽然这些肿瘤通常被认为具有惰性生长模式，但肿瘤亚群具有侵袭性病程。不幸的是，在单个患者中，没有临床、实验室或肿瘤组织学特征可以可靠地预测肿瘤是否会发展为侵袭性病程。此外，肠胰腺神经内分泌肿瘤发生和/或进展的分子机制在很大程度上是未知的。我们之前证明了正常胰岛细胞和胰岛素瘤细胞表达钙敏感受体（CaR），并且正常胰岛细胞和胰岛素瘤细胞对细胞外钙浓度变化的反应是不同的。为了探讨肠胰腺神经内分泌肿瘤的遗传和分子发病机制，我们分析了这些肿瘤的表达模式。我们对肿瘤样本的数据进行了分析，并提取了一些参与肿瘤淋巴结转移的候选基因。在这里，我们重点研究了候选基因中的细胞分化分子，包括NOTCH2和PDX1。PDX1、生长抑素和5 -羟色胺的表达模式与肿瘤的原发位置以及肿瘤以散发性或遗传性方式发生有关。PDX1在a115个十二指肠胃原质瘤中表达，而在4个胰腺肿瘤中表达降低。此外，PDX1在散发性肿瘤中不存在，在所有MEN1肿瘤中均有表达。这些基因表达模式的差异可能与肿瘤起源的不同有关。进一步研究细胞分化基因有助于明确肠胰腺神经内分泌肿瘤的靶基因及预后影响因素。如果能够确定分子预后因素，准确预测个体患者肿瘤的生长行为，则可以在预后较差的亚群中更早地开始更积极的治疗。少

Enteropancreatic neuroendocrine tumors constitute a wide variety of rare lesions that are named according to the hormones that they produce. Although these tumors generally are believed to have an indolent growth pattern, the subset of tumors have an aggressive course. Unfortunately, in an individual patient there are no clinical, laboratory, or tumor histological features that reliably predict which the tumor will pursue an aggressive course. Furthermore, the molecular mechanisms responsible for the development and/or progression of Enteropancreatic neuroendocrine tumors are largely unknown.We previously demonstrated that human normal islet cells and insulinoma cells express the calcium-sensing receptor (CaR), and that the response of normal islets and insulinoma cells to change in extracellular Ca concentration was different. To investigate the genetic and molecular pathogenesis of the enteropancreatic neuroendocrine tumors, we analyzed the expression patterns of these tumors. We' ob … More tained the analysis of the data from tumor samples and extracted the some candidate genes involved in nodal metastasis of tumors. Here, we focused on the cell differentiation molecules, including NOTCH2 and PDX1 from the candidate genes. The expression patterns of PDX1, somatostatin, and serotonin were associated with the primary location of the tumors and with the tumors occurring in a sporadic fashion or a hereditary fashion. PDX1 was expressed in a115 duodenal gastrinomas, whereas its expression was reduced in 4 pancreatic tumors. Furthermore, the PDX1 was absent in the tumor occurring in a sporadic fashion, and was expressed in all tumors with MEN1. The difference in expression pattern of these genes was possibly, caused by the different origin of the tumors. Further investigation of the cell differentiated genes could result in the identification of the target genes and prognostic factors in the enteropancreatic neuroendocrine tumor. If molecular prognostic factors could be identified that accurately predicted the growth behavior of tumors in an individual patient, more aggressive treatment could be started earlier in the subset with a poor prognosis. Less