Stein Johannes, Klümper Niklas, Zöhrer Pirmin, Büttner Thomas, Krausewitz Philipp, Ritter Manuel, Kristiansen Glen, Toma Marieta, Ellinger Jörg, Cox Alexander
Urology, University Hospital Bonn, University of Bonn, Bonn, DEU.
Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, University of Bonn, Bonn, DEU.
Cureus. 2024 Jan 27;16(1):e53038. doi: 10.7759/cureus.53038. eCollection 2024 Jan.
Ring finger proteins play pivotal roles in diverse cellular processes and are implicated in contribution to cancer. Ring finger protein 34 (RNF34) has antiapoptotic and oncogenic properties. RNF34 is upregulated during carcinogenesis and tumor progression in the colorectal adenoma-carcinoma sequence and was already described to mediate chemoresistance. In clear cell renal cell carcinoma (ccRCC), however, the role and expression patterns of RNF34 are unknown.
First, we investigated the association of RNF34 mRNA expression with clinicopathological parameters and survival using data obtained from The Cancer Genome Atlas (TCGA) ccRCC cohort (N = 533). To assess RNA34 protein expression, we performed immunohistochemical (IHC) staining of an established ccRCC cohort (University of Bonn) in a tissue microarray (TMA) format. This validation cohort contains 109 primary ccRCC samples. IHC data were associated with clinicopathological parameters and overall survival (Kaplan-Meier analysis). Adjustment for covariables was done using the Cox regression model.
RNF34 expression is correlated with adverse clinicopathological parameters. Survival analysis revealed an association between RNF34 expression and shortened survival. Cox regression analysis confirmed RNF34 expression as an independent prognostic parameter.
Our study provides evidence for RNF34 as a prognostic biomarker in ccRCC and points toward a major role of this protein in renal cell carcinoma carcinogenesis.
泛素连接酶在多种细胞过程中发挥关键作用,并与癌症的发生发展有关。泛素连接酶34(RNF34)具有抗凋亡和致癌特性。在结直肠癌腺瘤-癌序列的致癌过程和肿瘤进展中,RNF34表达上调,并且已被描述为介导化疗耐药。然而,在透明细胞肾细胞癌(ccRCC)中,RNF34的作用和表达模式尚不清楚。
首先,我们使用从癌症基因组图谱(TCGA)ccRCC队列(N = 533)获得的数据,研究RNF34 mRNA表达与临床病理参数及生存率之间的关联。为了评估RNA34蛋白表达,我们以组织微阵列(TMA)形式对一个已建立的ccRCC队列(波恩大学)进行免疫组织化学(IHC)染色。这个验证队列包含109个原发性ccRCC样本。IHC数据与临床病理参数及总生存率(Kaplan-Meier分析)相关。使用Cox回归模型对协变量进行调整。
RNF34表达与不良临床病理参数相关。生存分析显示RNF34表达与生存期缩短有关。Cox回归分析证实RNF34表达是一个独立的预后参数。
我们的研究为RNF34作为ccRCC的预后生物标志物提供了证据,并表明该蛋白在肾细胞癌发生中起主要作用。