通过基因表达研究鉴定原发性黏液样脂肪肉瘤转移相关基因特征

Zhiwei Qiao, Takashi Tajima, F. Kito, Y. Arai, A. Kawai, T. Kondo
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摘要

黏液样脂肪肉瘤(MLS)是一种罕见的间充质恶性肿瘤,具有独特的肺外转移潜力。虽然MLS与特定的染色体易位有关,但调节MLS转移的因素和途径仍不清楚。为了确定MLS转移的分子机制,我们使用DNA微阵列分析比较了不同转移状态的MLS患者原发肿瘤组织的整体基因表达谱。共有393个基因在4例转移患者和11例无转移患者的肿瘤中差异表达。基于京都基因与基因组百科全书(KEGG)通路分析对差异表达基因进行功能注释。基于393个基因的监督分类根据转移状态明确区分样本。负责转移的途径包括“局灶黏附”、“癌症途径”、“ecm受体相互作用”和“紧密连接”。在蛋白水平上证实了α -突触核蛋白的差异表达;该蛋白在转移性MLS中下调。荟萃分析显示,MLS可以根据转移相关基因的表达与其他肉瘤区分。本研究中发现的转移相关基因值得进一步研究,以进一步加深我们对MLS的理解,并有望为MLS带来新的临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metastasis-associated gene signature in primary myxoid liposarcoma identified through a gene expression study
Myxoid liposarcoma (MLS) is a rare mesenchymal malignancy with unique extrapulmonary metastatic potential. Although MLS has been associated with specific chromosomal translocations, the factors and pathways regulating metastasis in MLS remain unknown. To identify the molecular mechanisms underlying MLS metastasis, we compared global gene expression profiles of primary tumor tissues from MLS patients with different metastatic statuses using DNA microarray analysis. In total, 393 genes were differentially expressed between the tumors from four patients with metastasis and those from 11 patients without metastasis. Differentially expressed genes were functionally annotated based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Supervised classification based on the 393 genes clearly discriminated samples according to metastatic status. The pathways responsible for metastasis included “focal adhesion,” “pathways in cancer,” “ECM-receptor interaction,” and “tight junction.” The differential expression of alpha-synuclein was confirmed at the protein level; the protein was downregulated in metastatic MLS. Meta-analysis revealed that MLS could be discriminated from the other sarcomas based on the expression of the metastasis-associated genes. The metastasis-associated genes identified in this study are worthwhile further investigation to further our understanding of MLS and are expected to lead to novel clinical applications for MLS.
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