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FOXI1 expression in chromophobe renal cell carcinoma and renal oncocytoma: a study of The Cancer Genome Atlas transcriptome-based outlier mining and immunohistochemistry.
Virchows Archiv ( IF 3.5 ) Pub Date : 2020-08-19 , DOI: 10.1007/s00428-020-02900-x
Kuo Tong 1, 2, 3 , Zhongliang Hu 1, 3
Affiliation  

FOXI1 is a forkhead family transcription factor that plays a key role in differentiation and functional maintenance for the renal intercalated cell (IC). The diagnostic utility of FOXI1 is rarely studied thus far. Comparative analyses of FOXI1 mRNA expression in normal kidney tissue and different renal neoplasms including chromophobe renal cell carcinoma (chRCC), renal oncocytoma (RO), and other renal cell carcinomas were conducted using transcriptomic data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and single-cell RNA-seq datasets, in combination with integrative analyses using mutant data, karyotype data, and digital slides for cases with anomalous FOXI1 expression in TCGA. Formalin-fixed, paraffin-embedded whole-tissue slides of varied primary renal neoplasms (n = 367) were subjected to FOXI1 staining for validating FOXI1 transcription levels. We confirmed that FOXI1 was significantly upregulated at mRNA levels in ICs, chRCCs, and ROs compared with other renal tubule cell and renal cell carcinoma subtypes. Furthermore, most of the cases with FOXI1 expression outliers were misclassified in the TCGA kidney cancer project. An underlying novel entity with frequent mutations involved in the mTOR pathway was also found. FOXI1 immunoreactivity was consistently noted in ICs of the distal nephron. FOXI1 staining was positive in 85 of 93 chRCCs and 13 of 18 ROs, respectively. FOXI1 staining was not seen in renal neoplasms (n = 254) derived from non-ICs. In conclusion, FOXI1 expression in normal kidney tissue is restricted to ICs. This cell type–specific expression is retained during neoplastic transformation from ICs to chRCCs or ROs. FOXI1 is thereby a potential biomarker of IC-related tumors.



中文翻译:

FOXI1在发色肾细胞癌和肾肿瘤细胞瘤中的表达:基于癌症基因组图谱转录组的离群挖掘和免疫组织化学的研究。

FOXI1是一个叉头家族转录因子,在肾插层细胞(IC)的分化和功能维持中起关键作用。迄今为止,很少研究FOXI1的诊断工具。使用癌症基因组图谱(TCGA)的转录组数据,对正常肾脏组织和不同的肾脏肿瘤(包括发色性肾细胞癌(chRCC),肾癌细胞瘤(RO)和其他肾细胞癌)中的FOXI1 mRNA表达进行了比较分析。综合和单细胞RNA-seq数据集,结合使用突变数据,核型数据和数字幻灯片的综合分析,分析TCGA中FOXI1表达异常的情况。福尔马林固定,石蜡包埋的各种原发性肾脏肿瘤的全组织玻片(n = 367)进行FOXI1染色以验证FOXI1转录水平。我们证实,与其他肾小管细胞和肾细胞癌亚型相比,FOXI1在IC,chRCC和RO中的mRNA水平上显着上调。此外,在TCGA肾癌项目中,大多数具有FOXI1表达异常值的病例被错误分类。还发现了一个潜在的新颖实体,其频繁参与mTOR途径的突变。FOXI1免疫反应性始终在远端肾单位的IC中记录。FOXI1染色分别在93个chRCC中的85个和18个RO中的13个中呈阳性。在肾脏肿瘤中未观察到FOXI1染色(n = 254)来自非IC。总之,正常肾脏组织中的FOXI1表达仅限于IC。从IC到chRCC或RO的肿瘤转化过程中,这种细胞类型特异性表达得以保留。因此,FOXI1是IC相关肿瘤的潜在生物标志物。

更新日期:2020-08-19
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