CD44 Expression in Clear Cell Renal Cell Carcinoma (ccRCC) Correlates with Tumor Grade and Patient Survival and Is Affected by Gene Methylation

Sep 22, 2026

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Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, with surgery being the only potentially curative option, yet many patients relapse locally or with distant metastases. Using CD44 immunohistochemical staining on ccRCC patient samples and TCGA data analysis, the study characterizes CD44 expression patterns at mRNA and protein levels and links them to clinicopathological variables. CD44 expression correlates positively with higher tumor grade and worse overall survival, and CD44 mRNA upregulation is associated with reduced gene methylation, supporting epigenetic regulation in ccRCC development.

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CategoryHealthcare

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Abstract

Introduction

Materials and Methods

Tissue Specimens

Brief Report CD44 Expression in Clear Cell Renal Cell Carcinoma (ccRCC) Correlates with Tumor Grade and Patient Survival and Is Affected by Gene Methylation Anastasios D. Papanastasiou 1, *,†, Stavros Peroukidis 2,†, Chaido Sirinian 3, Elisavet Arkoumani 4, Dimitrios Chaniotis 1 and Adamantia Zizi-Sermpetzoglou 4 Citation: Papanastasiou, A.D.; Peroukidis, S.; Sirinian, C.; Arkoumani, E.; Chaniotis, D.; Zizi-Sermpetzoglou, A. CD44 Expression in Clear Cell Renal Cell Carcinoma (ccRCC) Correlates with Tumor Grade and Patient Survival and Is Affected by Gene Methylation. Genes 2024, 15, 537. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/genes15050537](10.3390/genes15050537) Academic Editors: Christophe Mariat and Guorong Li Received: 9 April 2024 Revised: 19 April 2024 Accepted: 23 April 2024 Published: 24 April 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece 2 Panarkadikon General Hospital, 22100 Tripolis, Greece 3 Molecular Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, 26504 Patras, Greece 4 Pathology Department, Tzaneion General Hospital of Piraeus, 18536 Piraeus, Greece * Correspondence: [apapanasta@uniwa.gr](apapanasta@uniwa.gr) † These authors contributed equally to this work. Abstract: Clear cell RCC (ccRCC) represents the most common type of kidney cancer, with surgery being the only potential curative treatment. Almost one-third of ccRCC patients relapse either locally or as cases of distant metastases. Several biomarkers have been employed in order to separate ccRCC patients with better prognosis or to predict treatment outcomes, with limited results. CD44 is a membrane glycoprotein with multiple roles in normal development but also cancer. Recently, the CD44 standard isoform has been implicated in tumor progression and the metastasis cascade through microenvironment interactions. Here, through CD44 immunohistochemical staining of ccRCC patient samples and TCGA data analysis, we sought to elucidate the expression patterns (mRNA and protein) of CD44 in clear cell RCC and correlate its expression with clinicopathological parameters. We were able to show that CD44 expression presents a positive association with tumor grade and overall survival, predicting a worse patient outcome in ccRCC. In addition, our data indicate that the CD44 mRNA upregulation can be attributed to reduced gene methylation, implicating epigenetic gene regulation in ccRCC development and progression. Keywords: CD44; renal cell carcinoma; immunohistochemistry 1. Introduction Renal cell carcinoma (RCC) accounts for 3% of all solid malignancies and is amongst the most lethal of urological cancers [1] . Clear cell RCC (ccRCC) represents the most common type of RCC, comprising approximately 60% of all renal tumors [2] . To date, the only potential curative treatment is surgery. However, 20–30% of patients with ccRCC develop local or distal recurrence within years of a nephrectomy [3] . The recurrence ofccRCC after surgery is a major factor that negatively affects patient survival. On the other hand, multiple unfavorable prognostic factors such as perineal fat invasion, tumor size as a continuous variable, size of the largest involved lymph node, and extra-nodal extension are neither reliable nor accurate enough for predicting the therapeutic response [4–6] . Recent studies have shown that a number of molecular and genetic biomarkers could play a role in predicting response to therapy [4,6,7] . CD44 glycoproteins are potentially important markers of tumor p

FAQs

How was CD44 expression evaluated in this study?

CD44 expression was assessed using immunohistochemical staining of ccRCC patient tissue samples and complementary TCGA data analysis to study mRNA and protein patterns.

What relationship did CD44 expression show with tumor grade and survival?

CD44 expression was positively associated with tumor grade and overall survival, indicating a worse patient outcome in ccRCC.

How does gene methylation relate to CD44 in ccRCC?

The data indicate that CD44 mRNA upregulation can be attributed to reduced gene methylation, suggesting epigenetic gene regulation in ccRCC progression.

Sep 22, 2026

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