Duodenopancreatic neuroendocrine tumors (DPNETs) aggressiveness is heterogeneous. Tumor grade and extension are commonly used for prognostic determination. Yet, grade classes are empirically defined, with regular updates changing the definition of classes. Genomic screening may provide more objective classes and reflect tumor biology. The aim of this study was to provide a transcriptome classification of DPNETs. We included 66 DPNETs, covering the entire clinical spectrum of the disease in terms of secretion, grade, and stage. Three distinct molecular groups were identified, associated with distinct outcomes (log-rank P < 0.01): (i) better-outcome DPNETs with pancreatic beta-cell signature. This group was mainly composed of well-differentiated, grade 1 insulinomas; (ii) poor-outcome DPNETs with pancreatic alpha-cell and hepatic signature. This group included all neuroendocrine carcinomas and grade 3 DPNETs, but also some grade 1 and grade 2 DPNETs and (iii) intermediate-outcome DPNETs with pancreatic exocrine and progenitor signature. This group included grade 1 and grade 2 DPNETs, with some insulinomas. Fibrinogen gene FGA expression was one of the topmost expressed liver genes. FGA expression was associated with disease-free survival (HR = 1.13, P = 0.005) and could be validated on two independent cohorts. This original pathophysiologic insight provides new prognostic classification perspectives.

中文翻译：

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十二指肠胰腺神经内分泌肿瘤的预后转录组分类。

十二指肠胰腺神经内分泌肿瘤 (DPNETs) 的侵袭性是异质的。肿瘤分级和扩展通常用于预后确定。然而，等级等级是凭经验定义的，定期更新会改变等级的定义。基因组筛查可以提供更客观的分类并反映肿瘤生物学。本研究的目的是提供 DPNETs 的转录组分类。我们纳入了 66 个 DPNET，涵盖了该疾病在分泌、分级和分期方面的整个临床谱。确定了三个不同的分子组，与不同的结果相关（对数秩 P < 0.01）：（i）具有胰腺 β 细胞特征的更好结果 DPNET。该组主要由分化良好的 1 级胰岛素瘤组成；(ii) 具有胰腺 α 细胞和肝脏特征的不良结果 DPNET。该组包括所有神经内分泌癌和 3 级 DPNET，但也包括一些 1 级和 2 级 DPNET，以及 (iii) 具有胰腺外分泌和祖细胞特征的中间结果 DPNET。该组包括 1 级和 2 级 DPNET，以及一些胰岛素瘤。纤维蛋白原基因FGA表达是表达最高的肝脏基因之一。FGA 表达与无病生存相关（HR = 1.13，P = 0.005），并且可以在两个独立的队列中进行验证。这种原始的病理生理学见解提供了新的预后分类观点。纤维蛋白原基因FGA表达是表达最高的肝脏基因之一。FGA 表达与无病生存相关（HR = 1.13，P = 0.005），并且可以在两个独立的队列中进行验证。这种原始的病理生理学见解提供了新的预后分类观点。纤维蛋白原基因FGA表达是表达最高的肝脏基因之一。FGA 表达与无病生存相关（HR = 1.13，P = 0.005），并且可以在两个独立的队列中进行验证。这种原始的病理生理学见解提供了新的预后分类观点。