Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis

Silviu Constantin Latcu; Razvan Bardan; Alin Adrian Cumpanas; Vlad Barbos; Flavia Baderca; Pusa Nela Gaje; Raluca Amalia Ceausu; Serban Comsa; Cristina-Stefania Dumitru; Raluca Dumache; Talida Georgiana Cut; Voichita Elena Lazureanu; Ligia Petrica

doi:10.3390/jpm14060557

Journal of Personalized Medicine (May 2024)

Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis

Silviu Constantin Latcu,
Razvan Bardan,
Alin Adrian Cumpanas,
Vlad Barbos,
Flavia Baderca,
Pusa Nela Gaje,
Raluca Amalia Ceausu,
Serban Comsa,
Cristina-Stefania Dumitru,
Raluca Dumache,
Talida Georgiana Cut,
Voichita Elena Lazureanu,
Ligia Petrica

Affiliations

Silviu Constantin Latcu: Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Razvan Bardan: Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Alin Adrian Cumpanas: Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Vlad Barbos: Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Flavia Baderca: Department II of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Pusa Nela Gaje: Department II of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Raluca Amalia Ceausu: Department II of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Serban Comsa: Department II of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Cristina-Stefania Dumitru: Department II of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Raluca Dumache: Department VIII, Discipline of Forensic Medicine, Bioethics, Deontology and Medical Law, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Talida Georgiana Cut: Center for Ethics in Human Genetic Identifications, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Voichita Elena Lazureanu: Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania
Ligia Petrica: Department of Internal Medicine II, Division of Nephrology, Victor Babes University of Medicine and Pharmacy Timisoara, County Emergency Hospital Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania

DOI: https://doi.org/10.3390/jpm14060557
Journal volume & issue: Vol. 14, no. 6
p. 557

Abstract

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Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms’ Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 − rho = 0.341, p-value = 0.036; TDs − rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs.

Published in Journal of Personalized Medicine

ISSN: 2075-4426 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/jpm

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