Thouënnon Erwan, Elkahloun Abdel G, Guillemot Johann, Gimenez-Roqueplo Anne-Paule, Bertherat Jérôme, Pierre Alice, Ghzili Hafida, Grumolato Luca, Muresan Mihaela, Klein Marc, Lefebvre Hervé, Ouafik L'Houcine, Vaudry Hubert, Plouin Pierre-François, Yon Laurent, Anouar Youssef
Institut National de la Santé et de la Recherche Médicale U413, Laboratory of Cellular and Molecular Neuroendocrinology, Institut Fédératif de Recherche Multidisciplinaires sur les Peptides 23, University of Rouen, 76821 Mont-Saint-Aignan, France.
J Clin Endocrinol Metab. 2007 Dec;92(12):4865-72. doi: 10.1210/jc.2007-1253. Epub 2007 Sep 18.
Pheochromocytomas are catecholamine-producing tumors that are generally benign but that can also present as or develop into malignancy. Occurrence of malignant pheochromocytomas can only be asserted by imaging of metastatic lesions.
We conducted a gene expression profiling of benign and malignant tumors to identify a gene signature that would allow us to discriminate benign from malignant pheochromocytomas and to gain a better understanding of tumorigenic pathways associated with malignancy.
A total of 36 patients with pheochromocytoma was studied retrospectively. There were 18 (nine benign and nine malignant) tumors used for gene expression profiling on pangenomic oligonucleotide microarrays.
We identified and validated a set of predictor genes that could accurately distinguish the two tumor subtypes through unsupervised clustering. Most of the differentially expressed genes were down-regulated in malignant tumors, and several of these genes encoded neuroendocrine factors involved in prominent characteristics of chromaffin cell biology. In particular, the expression of two key processing enzymes of trophic peptides, peptidylglycine alpha-amidating monooxygenase and glutaminyl-peptide cyclotransferase, was reduced in malignant pheochromocytomas.
The gene expression profiling of benign and malignant pheochromocytomas clearly identified a set of genes that could be used as a prognostic multi-marker and revealed that the expression of several genes encoding neuroendocrine proteins was reduced in malignant compared with benign tumors.
嗜铬细胞瘤是产生儿茶酚胺的肿瘤，通常为良性，但也可表现为恶性或发展为恶性。恶性嗜铬细胞瘤的发生只能通过转移病灶的影像学检查来确定。
我们对良性和恶性肿瘤进行了基因表达谱分析，以确定一种基因特征，使我们能够区分良性和恶性嗜铬细胞瘤，并更好地了解与恶性肿瘤相关的致瘤途径。
对36例嗜铬细胞瘤患者进行回顾性研究。其中18个肿瘤（9个良性和9个恶性）用于全基因组寡核苷酸微阵列的基因表达谱分析。
我们通过无监督聚类鉴定并验证了一组预测基因，这些基因可以准确区分两种肿瘤亚型。大多数差异表达基因在恶性肿瘤中下调，其中一些基因编码参与嗜铬细胞生物学突出特征的神经内分泌因子。特别是，恶性嗜铬细胞瘤中两种营养肽关键加工酶肽基甘氨酸α-酰胺化单加氧酶和谷氨酰胺基肽环化转移酶的表达降低。
良性和恶性嗜铬细胞瘤的基因表达谱分析明确鉴定出一组可作为预后多标记物的基因，并揭示与良性肿瘤相比，恶性肿瘤中几种编码神经内分泌蛋白的基因表达降低。
