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

基于基因表达谱分析有利于预测肾细胞癌生物学行为的生物标记。

• 批准号: 13670184
• 负责人: NAGASHIMA Yuji
• 金额: $ 2.18万
• 依托单位: YOKOHAMA CITY UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670184/
• 关键词: Renal cell carcinoma (RCC); cDNA Micro array; VHL gene; VEGF; HIF1?, 2?; adipophilin; IGFBP-3; マウクロアレイ

(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

（目的）肾细胞癌（RCC）包含多种具有明显不同临床特征和生物学行为的组织病理学亚型，因此，有必要针对每种病例制定策略性治疗方法，以获得更有利的临床结果。基于基因表达谱的肾细胞癌精确路径生物学诊断的生物标志物。（材料和方法）1 材料取自肾切除术的肾细胞癌组织和非肿瘤性肾组织。标本在横滨市立大学医院和附属医院进行分子生物学分析检查并获得患者的知情同意。2．常规程序，然后逆转录来自 RCC 和非肿瘤组织的 cDNA，分别用荧光染料标记，并使用测试芯片（测试 2 阵列，利用HuGeneFL阵列(Affirm etrix)进行微阵列分析。3．根据荧光强度的差异，分析RCC与非肿瘤组织、不同亚型RCC之间差异表达的基因。(结果)1．透明细胞 RCC 往往高度表达高保真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) 1α和2α被证实为adipophylin的优先表达。1．厌色性肾细胞癌和集合管癌显示出远端肾单位标志物E-钙粘蛋白的高表达。2．如果没有 von Hippel-Lindau (VHL) 疾病基因突变，则显示出更有利的结果具有基因突变的肾细胞癌。(结论)由于肾细胞癌不是一个统一的疾病实体，因此应仔细评估每个病例的生物学行为，基于此，脂肪亲和素和VHL基因突变被认为是研究肾细胞癌的重要标志物。

项目成果

Hamazaki S, Yao M, Nagashima Y, et al.: "Somatic von Hippel-Lindau gene mutation in a sporadic endolymphatic sac tumor"Hum Pathol. 32 11. 1272-1276 (2001)

Hamazaki S、Yao M、Nagashima Y 等人：“散发性内淋巴囊肿瘤中的体细胞 von Hippel-Lindau 基因突变”Hum Pathol。

Sakai N, Nagashima Y et al.: "SPARC expression in human primary renal cell carcinoma. Up-regulation of SPARC in sarcomatoid renal carcinoma"Hum Pathol. 32 10. 1064-1070 (2001)

Sakai N、Nagashima Y 等人：“人原发性肾细胞癌中的 SPARC 表达。肉瘤样肾癌中 SPARC 的上调”Hum Pathol。

Otani M, Shimaizu T, Serizawa T, Ebihara Y, Nagashima Y: "Low-grade renal cell carcinoma arising from the the lower nephron. A case report with immunohistochemical, histochemical and Ultrastructural studies."Pathol Int. 51(12). 956-960 (2001)

Otani M、Shimaizu T、Serizawa T、Ebihara Y、Nagashima Y：“源自下肾单位的低度肾细胞癌。免疫组织化学、组织化学和超微结构研究的病例报告。”Pathol Int。

Kondo K, Yao M, Yoshida M, Kishida K, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y and Hosaka M: "Comprehensive analysis of the VHL gene in sporadic renal cell carcinoma; relationsh

Kondo K、Yao M、Yoshida M、Kishida K、Shuin T、Miura T、Moriyama M、Kobayashi K、Sakai N、Kaneko S、Kawakami S、Baba M、Nakaikawa N、Nagashima Y、Nakatani Y 和 Hosaka M：“综合

Otain M, Tsujimoto S, Miyake M, Nagashima Y: "Intrarenalmature cystic teratoma associated with renal dysphasia: A case report with a review of literature."Pathol Int. 51(7). 560-563 (2001)

Otain M、Tsujimoto S、Miyake M、Nagashima Y：“与肾性言语障碍相关的肾内成熟囊性畸胎瘤：病例报告及文献综述。”Pathol Int。