Abstract：
Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study.
摘要：
胰腺神经内分泌癌（NEC）和混合性神经内分泌-非神经内分泌肿瘤（MiNEN）是罕见的胰腺恶性肿瘤。全面的基因分析很少。在这项研究中,收集了六个NEC和六个MINENs，突触素的免疫组织化学，嗜铬粒蛋白A,进行了INSM1、Ki-67和Rb，并检查了KRAS突变状态。在这些案例中,使用nCounter®对6个NEC和4个MiNEN进行了癌基因途径的综合基因表达分析，并将这些数据与三个胰腺导管腺癌（PDAC）的数据进行了比较，三个正常的胰管,和彼此。通过将NEC和MiNEN病例分为KRAS突变组和KRAS野生组，比较两组间临床病理资料和基因表达谱资料的差异。与正常胰腺上皮的数据相比，所有13个癌症相关通路在PDAC中上调，Minen,和NEC组有更多的上调顺序。与PDAC的数据相比，DNA损伤修复途径的基因在NECs和MINENs中表达最多。关于KRAS突变组和KRAS野生组之间的差异，两个基因有差异表达,其中MMP7是具有最高p值的上调基因，NKD1是KRAS突变组中具有最高p值的下调基因。从13种途径的上调程度来看，MiNEN被认为比PDAC更进步，NEC被认为比MiNEN进步更多。从KRAS突变和KRAS野生NECs和MINENs的比较来看，在这项研究中鉴定了几个差异表达的基因。
