Analysis of Gene Expression Identifies Differentially Expressed Genes and Pathways Associated with Lymphatic Dissemination in Patients with Adenocarcinoma of the Esophagus
Analysis of Gene Expression Identifies Differentially Expressed Genes and Pathways Associated with Lymphatic Dissemination in Patients with Adenocarcinoma of the Esophagus
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DOI：
10.1245/s10434-008-0165-y
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发表时间：
2008-12-01
影响因子：
3.7
通讯作者：
van Lanschot, J. J. B.
中科院分区：
文献类型：
--
作者：
Lagarde, S. M.;van Themaat, P. E. Ver Loren;van Lanschot, J. J. B.
引言：淋巴播散的存在是食管腺癌（EA）生存的一个重要预测因素。本研究的目的是发现食管腺癌淋巴播散的预后基因表达谱，并确定能为淋巴播散提供肿瘤学见解的基因和通路。
方法：将有淋巴播散的患者（N = 55）与无淋巴播散的患者（N = 22）进行比较。使用全基因组寡核苷酸微阵列评估77例食管癌的基因特征。采用多重随机验证来分析分子特征的稳定性和预测能力。应用基因集富集分析（GSEA）阐明肿瘤发生通路。
结果：在75±14%的淋巴结阳性患者中正确预测了淋巴播散。在41±23%的淋巴结阴性患者中正确预测了无淋巴播散。由于精氨琥珀酸合成酶（ASS）存在于大多数预后特征以及差异表达基因列表中，因此被选作蛋白质水平的验证。有淋巴播散的患者中ASS表达低于无淋巴播散的患者（P = 0.048）。GSEA确定精氨酸代谢通路和脂质代谢通路与发生淋巴播散的可能性较低有关。
讨论：该预测谱在预测食管腺癌患者淋巴播散的存在方面并不优于当前的临床实践。确定了几个在食管腺癌淋巴播散发展中起重要作用的基因，包括ASS，以及基因通路。
Introduction: The presence of lymphatic dissemination is an important predictor of survival in esophageal adenocarcinoma (EA). The aim of this study was to discover a prognostic gene expression pro. le for lymphatic dissemination in EA and to identify genes and pathways that provide oncological insight in lymphatic dissemination.Methods: Patients who had lymphatic dissemination (N = 55) were compared with patients without lymphatic dissemination (N = 22). Whole-genome oligonucleotide microarrays were used to evaluate the genetic signature of 77 esophageal cancers. Multiple random validation was used to analyze the stability of the molecular signature and predictive power. Gene set enrichment analysis (GSEA) was applied to elucidate oncogenetic pathways.Results: Lymphatic dissemination was correctly predicted in 75 +/- 14% of lymph node positive patients. The absence of lymphatic dissemination was correctly predicted in 41 +/- 23% of lymph-node-negative patients. Argininosuccinate synthetase (ASS) was selected for validation on the protein level because it was present in most prognostic signatures as well as the list of differentially expressed genes. ASS expression was lower (P = 0.048) in patients with lymphatic dissemination than in patients without. GSEA identified that arginine metabolism pathways and lipid metabolism pathways are related to less chance of developing lymphatic dissemination.Discussion: The predictive pro. le does not outperform current clinical practice to predict the presence of lymphatic dissemination in patients with EA. Several genes, including ASS, and genetic pathways which are important in the development of lymphatic dissemination in EA, were identified.