Ring Finger Protein 34 (RNF34) as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Johannes Stein; Niklas Klümper; Pirmin Zöhrer; Thomas Büttner; Philipp Krausewitz; Manuel Ritter; Glen Kristiansen; Marieta Toma; Jörg Ellinger; Alexander Cox

doi:10.7759/cureus.53038

Ring Finger Protein 34 (RNF34) as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Cureus. 2024 Jan 27;16(1):e53038. doi: 10.7759/cureus.53038. eCollection 2024 Jan.

Authors

Johannes Stein^{1

2}, Niklas Klümper^{1

2}, Pirmin Zöhrer^{1

2}, Thomas Büttner^{1

2}, Philipp Krausewitz^{1

2}, Manuel Ritter^{1

2}, Glen Kristiansen^{3

2}, Marieta Toma^{3

2}, Jörg Ellinger^{1

2}, Alexander Cox^{1

2}

Affiliations

¹ Urology, University Hospital Bonn, University of Bonn, Bonn, DEU.
² Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, University of Bonn, Bonn, DEU.
³ Pathology, University Hospital Bonn, University of Bonn, Bonn, DEU.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: biomarker; clear cell renal cell carcinoma; immunohistochemistry; renal cell carcinoma; rnf34; tcga.