Identification and validation of soluble carrier family expression signature for predicting poor outcome of renal cell carcinoma.
Identification and validation of soluble carrier family expression signature for predicting poor outcome of renal cell carcinoma.
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可溶性载体家族表达特征的鉴定和验证用于预测肾细胞癌的不良预后
DOI：
10.7150/jca.18257
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发表时间：
2017
影响因子：
3.9
通讯作者：
Dingwei Y
中科院分区：
文献类型：
--
作者：
Fangning W;Chunguang M;Hailiang Z;Guohai S;Yao Z;Bo D;Yijun S;Yiping Z;Dingwei Y
可溶性载体（SLC）家族在细胞代谢中起重要作用。本研究的目的是筛选SLC作为肾透明细胞癌（ccRCC）的潜在预后因素。来自癌症基因组图谱（TCGA）队列的总计509例ccRCC患者入组本研究。从TCGA RNAseq数据库获得SLC的表达谱。收集TCGA队列的元数据，包括年龄、性别、TNM分期、肿瘤分级、美国癌症联合委员会分期、偏侧性和总生存期。采用单因素和多因素考克斯比例风险回归模型分析相关因素。在复旦大学上海肿瘤中心（FUSCC）的178例患者队列中进一步验证了预后相关基因。在总共364个SLC转运蛋白中，61个是ccRCC患者总生存期的独立预测因子。在61个SLC转运体中，与非恶性肾组织相比，26个在肿瘤组织中显著下调，23个显著上调。对两个开放源的舒尼替尼反应的RNA表达数据集的分析显示，SLC 10A 2在酪氨酸激酶受体耐药样品中下调。我们在FUSCC队列中验证了SLC 10A 2表达，并表明SLC 10A 2表达是ccRCC总生存期的独立预后预测因子（风险比=0.432，95%CI：0.204-0.915）。我们的研究结果确定了SLC基因表达与ccRCC患者预后的一些相关性，表明这些基因可能代表可能作为ccRCC治疗靶点的可能癌基因。
The soluble carrier (SLC) family plays an important role in cell metabolism. The purpose of the current study was to screen SLCs as potential prognostic factors in clear cell renal cell carcinoma (ccRCC). A total of 509 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort were enrolled in this study. The expression profile of SLCs was obtained from the TCGA RNAseq database. Metadata of the TCGA cohort, including age, sex, TNM stage, tumor grade, American Joint Committee on Cancer stage, laterality, and overall survival, were collected. Univariate and multivariate Cox proportional hazards regression models were used to analyze the relative factors. Prognosis-associated genes were further validated in a Fudan University Shanghai Cancer Center (FUSCC) cohort consisting of 178 patients. Among a total of 364 SLC transporters, 61 were independent predictors of ccRCC patient overall survival. Among the 61 SLC transporters, 26 were significantly downregulated and 23 were significantly upregulated in tumor tissues compared with non-malignant kidney tissues. Analyses of two open source, RNA expression data sets on sunitinib response revealed that SLC10A2 was downregulated in tyrosine kinase inhibitor-resistant samples. We validated SLC10A2 expression in the FUSCC cohort and showed that SLC10A2 expression was an independent prognostic predictor of overall survival of ccRCC (hazard ratio=0.432, 95% CI: 0.204-0.915). Our results identified a number of associations of SLC gene expression with prognosis of ccRCC patients, indicating that these genes may represent possible oncogenes that could serve as therapeutic targets of ccRCC.
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DOI：
10.1158/1078-0432.ccr-14-2031
发表时间：
2015-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Zhang L;Wang X;Bullock AJ;Callea M;Shah H;Song J;Moreno K;Visentin B;Deutschman D;Alsop DC;Atkins MB;Mier JW;Signoretti S;Bhasin M;Sabbadini RA;Bhatt RS
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