ANALYSIS OF BIOLOGICAL MARKERS BENEFICIAL TO PREDICT BIOLOGIC BEHAVIOR S OF THE RENAL CELL CARCINOMAS BASED ON GENE EXPRESSION PROFILING.

肾细胞癌（renal cell carcinoma，RCCs）是一组临床特征和生物学行为明显不同的病理亚型。因此，有必要为每个病例制定策略性治疗，以获得更有利的临床结局。本研究的目的是探索基于基因表达谱的肾癌精确路径生物学诊断的有用生物学标记。（材料和方法）1.材料; RCC组织和同时非肿瘤性肾组织从横滨市立大学医院和附属医院进行的肾切除标本中获得。在分子生物学分析检查时获得患者的知情同意。收集的样品储存在液氮中直至使用。按常规方法提取总RNA，进行反转录。分别从肾细胞癌组织和非肿瘤组织中提取cDNA， ...更多信息 用荧光染料染色。使用测试芯片（测试2阵列，Affirm公司）确认其质量的cDNA，使用HuGeneFL阵列（Affirm公司）进行微阵列分析。根据荧光强度的差异，分析肾癌与非肿瘤组织之间以及不同亚型肾癌之间差异表达的基因。（结果）1.透明细胞RCC倾向于高表达嗜听细胞、胰岛素样生长因子结合蛋白（IGFBP3）、血管内皮生长因子（VEGF）和缺氧诱导因子（HIF）1 α和2 α。免疫组化证实了脂肪叶蛋白的优先表达。嫌色肾癌和集合管癌中E-cadherin的表达高，E-cadherin是远端肾单位的标志.同时对肾细胞癌伴和不伴VHL基因突变的患者进行临床病理学研究，发现伴VHL基因突变的肾细胞癌预后更好。（结论）由于肾细胞癌不是一个统一的疾病实体，应仔细评估其生物学行为。基于此，adipophilin和VHL基因突变被认为是研究RCC的重要标志。少

(OBJECT)Renal cell carcinomas (RCCs) contain several histopathological subtypes with markedly different clinical features and biological behaviors. Therefore, establishment of strategic treatments is necessary for each cases to obtain more favorable clinical outcomes. In this research, we aimed to exploration of useful biological marker for precise path biological diagnosis of RCCs based on gene expression profiling.(MATERIALS AND METHODS)1. Materials; RCC tissues and simultaneously nonneoplastic renal tissues were obtained from nephrectomy specimens performed at the Yokohama City University Hospital and the affiliated hospitals. Informed consents were obtained from the patients on examination of the molecular biological analyses. The collected samples were stored in liquid nitrogen until use.2. Total RNAs were extracted from the materials according to the routine procedures, and then reverse-transcribed. The resultant cDNAs derived from RCC and nonneoplastic tissues were separately la … More beled with fluorescent dyes. The cDNAs of which qualities were confirmed using the Test Chip (Test 2 array, Affirm etrix), were subjected to micro array analyses using HuGeneFL array (Affirm etrix).3. Based on differences of the fluorescent intensities, genes differently expressed were analyzed between RCCs and nonneoplastic tissues, and among RCCs of different subtypes.(RESULTS)1. Clear cell RCCs tended to highly express audiophile, insulin-like growth factor binding protein (IGFBP3), vascular endothelial growth factor (VEGF) and hypoxia-inducible factors(HIFs) 1αand 2α. Immunohistochemically, preferential expression Is confirmed for adipophylin.1. Chromophobe RCCs and collecting duct carcinoma showed high expression for E-cadherin, a marker for the distalnephron.2. Simultaneously preformed Clinicopathological study form RCC with and without von Hippel-Lindau (VHL) disease gene mutation revealed more favorable outcome in RCCs with gene mutation.(CONCLUSION)Because RCCs are not a uniform disease entity, biological behaviors in each case should be carefully evaluated. Based on this fact, adipophilin and VHL gene mutations were considered to be important marker to investigate RCCs. Less