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长链非编码RNA HOTAIR的异常表达及同源13个HOX基因的失调与胃肠胰神经内分泌肿瘤的侵袭性行为密切相关。

Aberrant Expression of Long Non Coding RNA HOTAIR and De-Regulation of the Paralogous 13 HOX Genes Are Strongly Associated with Aggressive Behavior of Gastro-Entero-Pancreatic Neuroendocrine Tumors.

作者信息

Di Mauro Annabella, Scognamiglio Giosuè, Aquino Gabriella, Cerrone Margherita, Liguori Giuseppina, Clemente Ottavia, Di Bonito Maurizio, Cantile Monica, Botti Gerardo, Tafuto Salvatore, Tatangelo Fabiana

机构信息

Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Via Mariano Semmola, 80131 Naples, Italy.

Sarcomas and Rare Tumors Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy.

出版信息

Int J Mol Sci. 2021 Jun 30;22(13):7049. doi: 10.3390/ijms22137049.

DOI:10.3390/ijms22137049
PMID:34208964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8268982/
Abstract

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.

摘要

胃肠胰神经内分泌肿瘤（GEP-NENs）是发生于胃肠道和胰腺的罕见疾病。它们的特征是上皮管状腺成分缺失，以及神经内分泌标志物表达增加。GEP-NENs分为两种组织病理学类型，即胃肠胰神经内分泌瘤（GEP-NETs）和胃肠胰神经内分泌癌（GEP-NECs）。根据世界卫生组织2017年和2019年的分类标准，分为NET-G1、NET-G2、NET-G3和NEC-G3四类进行分级和分期。这些肿瘤的分子特征对于鉴定新的诊断、预后和预测生物标志物可能至关重要。本研究的主要目的是分析同源的13个HOX基因（通常参与胚胎发育且在人类癌症中经常失调）以及HOX调节lncRNA在GEP-NENs中的表达。在从GEP NET G1肿瘤向NET/NEC G3肿瘤的转变过程中，HOX基因的表达逐渐丧失，而与HOX基因表达呈负相关且在低级别GEP NENs中弱表达的[具体基因名称未明确，原文表述有误，推测可能是某个基因]在NET G3和NEC G3类别中变得异常。我们的数据通过提出新的预后标志物和潜在治疗靶点，突出了它们在GEP-NENs分子分层中的潜在作用。

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