Discovery of targets for treatment with renal cell carcinoma by gene and protein expression profile analysis

肾细胞癌（Renal cell carcinoma，RCC）是对化疗或放疗最具抵抗力的恶性肿瘤之一，因此，标准治疗是手术治疗。此外，没有有效的生物标志物用于诊断。为了阐明肾癌的耐药机制，寻找新的治疗靶点和诊断标志物，本研究对肾癌及其癌旁正常组织进行了转录组和蛋白质组分析，发现sorcin在肾癌组织中的表达较低，因此我们利用RNA干扰技术研究了sorcin在肾癌增殖中的作用。在肾细胞癌细胞Caki-1中，通过使用siRNA敲低sorcin发现血管内皮生长因子（VEGF）的上调，VEGF是一种促进癌症增殖的有效血管生成因子。为了综合分析肾癌组织及癌旁正常组织中的蛋白表达情况，用含6个碳原子的2-硝基苯磺酰氯（2-nitrobeazensulfonylchloride，2-nitrobeazensulfonylchloride）标记肾癌组织及癌旁正常<12><13>组织。然后进行MALDI-TOF/MS分析，对相差6 Da的成对峰进行鉴定。除了已知的蛋白质外，还鉴定了未知的蛋白质，这些蛋白质已被报道在RCC中上调。

Renal cell carcinoma (RCC) is one of the most chemotherapy or radiotherapy-resistant malignant tumors, and therefore, the standard therapy is surgical treatment. Also, there is no efficient biomarker for diagnosis. To elucidate resistant mechanisms and discovery novel targets for treatment and biomarker for diagnosis, transcriptome and proteome analysis were carried out using RCC and adjacent normal tissues.Since lower expression of sorcin in RCC was found, we investigated its role in cancer proliferation by RNA interference. Up-regulation of vascular endothelial growth factor (VEGF), a potent angiogenesis factor contributing to cancer proliferation, was found by knock-down of sorcin using siRNA in renal cell carcinoma cells, Caki-1. This suggested that lower expression of sorcin caused up-regulation of VEGF, thereby lead cancer proliferation.To comprehensive analysis of protein expressions in RCC and adjacent normal tissues, samples were labeled with 2-nitrobeazenesulfonyl chloride with six ^<12>C or ^<13>C atoms. Then, they were applied MALDI-TOF/Ms and pair peak of 6 Da difference were analyzed and identified. Unknown proteins were identified in addition to known proteins, which have been reported to be up-regulated in RCC.