Objective:To investigate the value of tumor budding in the clinicopathology and prognosis of pancreatic neuroendocrine tumors.Methods:The Cliniccal data of 105 pancreatic neuroendocrine tumor patients underwent resection in Henan Provincial People's Hospital from Jan 2010 to Dec 2016 were retrospectively analyzed. Tumor budding was calculated through hematoxylin-eosin (HE) and immunohistochemical stained slides. Based on the receiver operating characteristic curve (ROC), the number of tumor budding ≥10 was defined as the high-grade budding group, and <10 as the low-grade budding group. Multiple analysis was performed to determine the relationship between tumor budding and clinicopathology as well as prognosis.Results:High-grade budding group was observed in 35 cases and low-grade group in 70. High-grade budding were more common in tumors with advanced T stage, high risk of lymphatic metastasis, preoperative liver metastasis, vascular invasion and postoperative recurrence (respectively χ 2=9.043, 4.286, 10.130, 12.090, 9.260, all P<0.05). Multivariate COX regression analysis showed that tumor budding ( P=0.018), tumor grade ( P=0.026), preoperative liver metastasis ( P=0.042), vascular invasion( P=0.048) was independent risk factors predicting poor prognosis. Conclusion:Tumor budding is highly correlated with clinicopathological parameters which reflect the aggressiveness of pancreatic neuroendocrine tumor, it is also an important prognostic factor.

Background Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets. Methods Tumor samples of three DPC patients were collected and integrating RNA-seq analysis of tumor tissues and matched normal tissues were performed to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out to understand the potential bio-functions of the DPC differentially expressed genes (DEGs). Protein–protein interaction (PPI) network was constructed for functional modules analysis and identification of hub genes. qRT-PCR of clinical samples was conducted to validate the expression level of the hub genes. Results A total of 110 DEGs were identified from our RNA-seq data, GO and KEGG analyses showed that the DEGs were mainly enriched in multiple cancer-related functions and pathways, such as cell proliferation, IL-17signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway. The PPI network screened out five hub genes including IL-6, LCN2, FABP4, LEP and MMP1, which were identified as core genes in the network and the expression value were validated by qRT-PCR. The hub genes identified in this work were suggested to be potential therapeutic targets of DPC. Discussion The current study may provide new insight into the exploration of DPC pathogenesis and the screened hub genes may serve as potential diagnostic indicator and novel therapeutic target.

BACKGROUND:Although pancreatic neuroendocrine tumors (PNETs) are considered indolent tumors, nearly half of cases metastasize to the liver, which can be lethal. However, effective indicators to predict aggressive behavior have not been well-established. METHODS:In the current study, we explored the prognostic significance of tumor budding in Grade 1-2 PNETs. Hematoxylin-eosin and immunohistochemically stained slides of surgically removed Grade 1-2 PNETs were evaluated. RESULTS:Tumor budding, a histomorphological parameter that corresponds to single cells or small cell clusters (<5 cells), was classified as low (0-10 buds) and high (>10 buds) grade. We observed that tumor budding was correlated with aggressive histopathological parameters, such as T stage, lymph node status, metastasis, and vascular invasion (p < .05). Univariate and multivariate analyses showed that high-grade budding was an independent predictive factor for postoperative liver metastasis (p = .012). Moreover, Grade 1-2 PNETs with high-grade budding was associated with worse overall survival and disease-free survival (p = .0015 and p = .0041, respectively). CONCLUSIONS:We conclude that tumor budding may serve as a valuable parameter in the risk stratification of postoperative liver metastasis and that incorporating tumor budding into histopathological reports may aid in appropriate clinical management.