复发转移高危人群是影响胰腺神经内分泌瘤（PanNET）预后的关键，PanNET微血供丰富，且微血管越丰富的PanNET越不易发生转移，其机制尚不明确。我们前期构建了PanNET复发风险分层，筛选出复发转移高危患者；同时发现PanNET预后与微血管密度、PDGFR-β＋周细胞微血管完整性和MEN1突变显著相关，且MEN1突变导致PI3K及pAkt表达上调和微血管完整性改变。我们推测：MEN1突变通过上调PI3K/Akt通路提高PDGFR-β＋周细胞微血管完整性，减少肿瘤转移提高预后。本项目拟采用免疫组化、免疫荧光等检测周细胞微血管完整性。体内外实验检测MEN1、PI3K/Akt通路表达，干预实验检测调控MEN1及PI3K/Akt通路对周细胞微血管完整性和PanNET侵袭转移的影响，进而明确MEN1突变通过Akt/mTOR通路调控微血管完整性影响PanNET侵袭转移的机制。

High recurrence risk is essential for pancreatic neuroendocrine tumors (PanNET), PanNET are characteristically hypervascular, the less malignant neuroendocrine tumors is, the more microvascular angiogenesis, the mechanism is not yet clear. We built a recurrence risk stratification of PanNET and identified patients with high recurrence risk. We found that patients with high recurrence risk had lower PDGFR-β + pericytes microvascular integrity and low expression of PI3K and pAkt, and MEN1 gene mutation was associated with PanNET prognosis and microvascular integrity. We hypothesize that the MEN1 mutation up-regulates the PDGFR-β + pericytes microvascular integrity via PI3K/Akt pathway, inhibits tumor metastasis and improves prognosis. We intends to detect MEN1, PI3K/Akt pathway expression via immunohistochemistry, and detect pericyte microvascular integrity via Immunofluorescence, and use cellular co-culture and animal experiments to analyze the role of MEN1 on the microvascular integrity and the invasion of neuroendocrine tumors through the PI3K/Akt pathway, through the study we want to clarify the mechanism of MEN1 mutation regulate microvascular integrity and metastasis of PanNET through the PI3K/Akt pathway.