Molecular classification of renal tumors by gene expression profiling
Molecular classification of renal tumors by gene expression profiling
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DOI：
10.1016/s1525-1578(10)60547-8
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发表时间：
2005-05-01
影响因子：
4.1
通讯作者：
Young, AN
中科院分区：
文献类型：
--
作者：
Schuetz, AN;Yin-Goen, Q;Young, AN
肾肿瘤的分类很重要，因为组织病理学亚型与不同的临床行为相关。然而，诊断是困难的，因为肿瘤亚型有重叠的显微镜特征。因此，需要辅助方法来优化分类。我们使用寡核苷酸微阵列分析了31例成人肾肿瘤，包括透明细胞肾细胞癌（RCC）、乳头状肾细胞癌、憎色肾细胞癌、嗜瘤细胞瘤和血管平滑肌脂肪瘤。表达谱与组织病理学相关；无监督算法根据适当的诊断亚型对31个肿瘤中的30个进行聚类，而监督分析确定了显著的亚型特异性表达标记。透明细胞RCC过表达近端肾元、血管生成和免疫应答基因，嗜色细胞RCC过表达远端肾元和氧化磷酸化基因，乳头状RCC过表达。丝氨酸蛋白酶抑制剂、细胞外基质产物和血管平滑肌脂肪瘤过度表达肌肉发育、脂质生物合成、黑素细胞和不同的血管生成因子。定量逆转录-聚合酶链反应和福尔马林固定肾肿瘤的免疫组织化学证实，透明细胞和乳头状肾细胞癌中近端肾单位标记物（meggalin /低密度脂蛋白相关蛋白2，a-甲基酰基辅酶a消旋酶）和远端肾单位标记物（β -防御素1，claudin 7）在厌色肾细胞癌/癌细胞瘤中过表达。总之，肾肿瘤亚型通过不同的基因表达谱进行分类，阐明了肿瘤病理生物学，并转化为使用固定组织的新型分子生物测定方法。
Renal tumor classification is important because histopathological subtypes are associated with distinct clinical behavior. However, diagnosis is difficult because tumor subtypes have overlapping microscopic characteristics. Therefore, ancillary methods are needed to optimize classification. We used oligonucleotide microarrays to analyze 31 adult renal tumors, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma. Expression profiles correlated with histopathology; unsupervised algorithms clustered 30 of 31 tumors according to appropriate diagnostic subtypes while supervised analyses identified significant, subtype-specific expression markers. Clear cell RCC overexpressed proximal nephron, angiogenic, and immune response genes, chromophobe RCC oncocytoma overexpressed distal nephron and oxidative phosphorylation genes, papillary RCC overexpressed. serine protease inhibitors, and extracellular matrix products, and angiomyolipoma overexpressed muscle developmental, lipid biosynthetic, melanocytic, and distinct angiogenic factors. Quantitative reverse transcriptase-polymerase chain reaction and inimunohistochemistry of formalin-fixed renal tumors confirmed overexpression of proximal nephron markers (megalin/low-density lipoprotein-related protein 2, a-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron markers (beta-defensin 1, claudin 7) in chromophobe RCC/oncocytoma. in summary, renal tumor subtypes were classified by distinct gene expression profiles, illustrating tumor pathobiology and translating into novel molecular bioassays using fixed tissue.