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

肾细胞癌(RCC)是对化疗或放疗耐药最严重的恶性肿瘤之一，因此，标准的治疗方法是手术治疗。此外，目前还没有有效的生物标志物来诊断。为了阐明肾癌的耐药机制，发现新的治疗靶点和诊断的生物标志物，我们对肾癌和癌旁正常组织进行了转录组和蛋白质组分析。由于在肾癌组织中发现sorcin的表达较低，我们通过RNA干扰来研究其在肿瘤增殖中的作用。血管内皮生长因子(VEGF)是一种促进肿瘤增殖的有效血管生成因子，通过使用siRNA下调肾细胞癌细胞CAKI-1中的索尔菌素，发现其上调。为了综合分析肾癌和癌旁正常组织中的蛋白表达，用6个^&lt；12&gt；C或^&lt；13&gt；C原子标记2-亚硝基苯磺酰氯。然后，应用MALDI-TOF/MS，分析和鉴定了6 Da差的双峰。除了已知的蛋白外，还发现了未知的蛋白，据报道，这些蛋白在肾癌中上调。

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.