Zhang Limin, Jiang Haowen, Xu Gang, Wen Hui, Gu Bin, Liu Jun, Mao Shanghua, Na Rong, Jing Yan, Ding Qiang, Zhang Yuanfang
Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Mol Med Rep. 2015 Jun;11(6):4093-100. doi: 10.3892/mmr.2015.3321. Epub 2015 Feb 9.
In order to investigate the two members of the EF‑hand Ca2+ binding protein S100 family, S100A8 and S100A9, in renal cell carcinoma (RCC), serum samples were collected from patients with RCC, transitional cell carcinoma in the kidney, benign renal masses and normal controls. The samples were analyzed by isobaric tags for relative and absolute quantification technology to identify the differential expression of S100A8 and S100A9 in the respective groups. Hierarchical clustering analysis was then conducted for the samples and the relevant selected gene. The cross‑platform analysis for the external validation was performed by means of The Cancer Genome Atlas database, containing the gene/microRNA expression pattern and clinical information of patients with RCC. Immunohistochemical staining was used to verify the expression of S100A8 and S100A9 in the four groups. As a result, serum and mRNA expression levels of S100A8 and S100A9 were found to be upregulated in patients with RCC compared with the other three groups, which was consistent with the result of the upregulated expression of mRNA levels in RCC tissue. The overexpression of S100A8 and S100A9 in cancer cells was also confirmed by immunohistochemistry. In addition, bioinformatics revealed that let‑7, a microRNA formerly identified as an inhibiting factor of RCC was downregulated in RCC, which contrasted with S100A8. It was also complementary to the sequence at the 3' untranslated region terminal of S100A8. Therefore, indicating that S100A8 and S100A9 may serve as biomarkers for the detection of RCC.
为了研究EF手型钙离子结合蛋白S100家族的两个成员S100A8和S100A9在肾细胞癌(RCC)中的作用,收集了肾细胞癌患者、肾移行细胞癌患者、肾良性肿块患者及正常对照者的血清样本。采用等压标签相对和绝对定量技术对样本进行分析,以确定S100A8和S100A9在各组中的差异表达。然后对样本和相关选定基因进行层次聚类分析。通过癌症基因组图谱数据库进行外部验证的跨平台分析,该数据库包含肾细胞癌患者的基因/微小RNA表达模式和临床信息。采用免疫组织化学染色法验证S100A8和S100A9在四组中的表达情况。结果发现,与其他三组相比,肾细胞癌患者血清和mRNA中S100A8和S100A9的表达水平上调,这与肾细胞癌组织中mRNA水平上调的结果一致。免疫组织化学也证实了癌细胞中S100A8和S100A9的过表达。此外,生物信息学显示,曾被确定为肾细胞癌抑制因子的微小RNA let-7在肾细胞癌中表达下调,这与S100A8相反。它也与S100A8 3'非翻译区末端的序列互补。因此,表明S100A8和S100A9可能作为肾细胞癌检测的生物标志物。