otoferlin是透明细胞肾细胞癌患者的一种预后生物标志物：一项系统表达分析。

Otoferlin is a prognostic biomarker in patients with clear cell renal cell carcinoma: A systematic expression analysis.

作者信息

Cox Alexander, Tolkach Yuri, Stein Johannes, Kristiansen Glen, Ritter Manuel, Ellinger Jörg

机构信息

Department of Urology, University Hospital Bonn, Bonn, Germany.

Institute of Pathology, University Hospital Bonn, Bonn, Germany.

出版信息

Int J Urol. 2021 Apr;28(4):424-431. doi: 10.1111/iju.14486. Epub 2021 Jan 19.

DOI:10.1111/iju.14486

PMID:33465825

Abstract

OBJECTIVES

To comprehensively investigate the role of otoferlin as a prognostic and diagnostic biomarker in clear cell renal cell carcinoma.

METHODS

Three independent cohorts were used to study otoferlin in clear cell renal cell carcinoma: The Cancer Genome Atlas cohort (messenger ribonucleic acid expression; clear cell renal cell carcinoma n = 514, normal renal tissue n = 81); study validation cohort (messenger ribonucleic acid expression; clear cell renal cell carcinoma n = 79, normal renal tissue n = 44); and immunohistochemistry cohort (protein expression; clear cell renal cell carcinoma n = 142, normal renal tissue n = 30). Otoferlin gene expressions were extracted from The Cancer Genome Atlas database or determined using quantitative real-time polymerase chain reaction, respectively. Protein expression was assessed using immunohistochemistry staining against otoferlin on tissue microarrays. Correlations between otoferlin messenger ribonucleic acid/protein expression and clinicopathological data/patient survival were statistically tested.

RESULTS

Otoferlin messenger ribonucleic acid expression was significantly upregulated in clear cell renal cell carcinoma compared with normal renal tissue. High expression levels correlated with advanced stage, higher grade and metastatic tumors, accompanied by independent prognostic significance for overall and cancer-specific survival. In contrast, otoferlin protein expression was downregulated in tumor tissue. Although, high otoferlin expression in clear cell renal cell carcinoma was positively correlated with histological grading and independently predictive of a shortened progression-free survival.

CONCLUSION

Our data suggest otoferlin as an indicator of tumor aggressiveness and as a prognostic biomarker for patients with clear cell renal cell carcinoma, leading to the conclusion that otoferlin could promote the malignancy of clear cell renal cell carcinoma.

摘要

目的

全面研究 otoferlin 作为透明细胞肾细胞癌预后和诊断生物标志物的作用。

方法

使用三个独立队列研究透明细胞肾细胞癌中的 otoferlin：癌症基因组图谱队列（信使核糖核酸表达；透明细胞肾细胞癌 n = 514，正常肾组织 n = 81）；研究验证队列（信使核糖核酸表达；透明细胞肾细胞癌 n = 79，正常肾组织 n = 44）；以及免疫组织化学队列（蛋白质表达；透明细胞肾细胞癌 n = 142，正常肾组织 n = 30）。分别从癌症基因组图谱数据库中提取或使用定量实时聚合酶链反应测定 otoferlin 基因表达。使用针对组织微阵列上的 otoferlin 的免疫组织化学染色评估蛋白质表达。对 otoferlin 信使核糖核酸/蛋白质表达与临床病理数据/患者生存之间的相关性进行统计学检验。

结果

与正常肾组织相比，透明细胞肾细胞癌中 otoferlin 信使核糖核酸表达显著上调。高表达水平与晚期、高分级和转移性肿瘤相关，对总生存和癌症特异性生存具有独立的预后意义。相比之下，肿瘤组织中 otoferlin 蛋白表达下调。尽管如此，透明细胞肾细胞癌中高 otoferlin 表达与组织学分级呈正相关，并且独立预测无进展生存期缩短。