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Gene expression and oxidative stress markers profile associated with toxic metals in patients with renal cell carcinoma

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Abstract

Background

Toxic metals are associated with cancer progression. Studies have reported the relation between some toxic metals and renal cell carcinoma (RCC).

Methods and results

Blood levels of Cd and Pb were determined in 94 RCC patients (RCC group) and 91 matched controls as well as blood level of malondialdehyde (MDA) and catalase (CAT) activity as markers of oxidative stress and antioxidant, respectively. Gene expression of MAP kinase pathway (P38 and JNK), hypoxia-inducible factor 1-alpha (HIF1α), vascular endothelial growth factor (VEGF), cytochrome C oxidase subunit 6 (COX6), metallothionein (MT2A), and heat shock protein (HSP90AA1) were evaluated in the obtained tissue specimens. Blood Cd and Pb levels were significantly higher in RCC group comparing to control group with preferential significant increase of Cd in chromophobe RCC (chRCC) sub-type. MDA level was significantly higher and CAT activity was lower in the RCC compared to controls. The difference was evident only in chRCC. The expressions of genes were significantly increased in the cancer tissues than in non-cancerous tissues in RCC sub-types and there was a significant correlation between Cd levels and expression of genes VEGF, MT2A, P38 and JNK in chRCC group. Immunohistochemical staining of clear cell RCC tissues shows a marked expression of VEGF and HIF-1α.While COX6 staining show marked expression in chRCC.

Conclusions

There is a positive correlation between Cd toxicity and the development of RCC, especially chRCC sub-type. Cd is strongly incriminated in the pathogenesis of chRCC through the effort on some genes and oxidative stress markers.

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All data and materials are available if requested.

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Acknowledgements

We would like to thank Ministry of Higher Education in Egypt for the financial support of this study.

Funding

This work was funded by Ministry of Higher Education, Egypt (Gant # CEP1-031-MANS).

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Authors and Affiliations

  1. Department of Chemistry, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt

    Heba H. Tarabay & A. F. Abdel-Aziz

  2. Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, PO: 135516, Mansoura, 35516, Egypt

    Hassan Abol-Enein & Amira Awadalla

  3. Clinical Chemistry Laboratory, Urology and Nephrology Center, Mansoura University, Mansoura, 35516, Egypt

    Wael I. Mortada

Authors
  1. Heba H. Tarabay
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  2. Hassan Abol-Enein
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  3. Amira Awadalla
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  4. Wael I. Mortada
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  5. A. F. Abdel-Aziz
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Contributions

HHT Methodology and writing the original draft. HAE Supplied the tissue and blood sample, reviewed the manuscript and supervision. AA Designed the research and methodology. WIM Formal analysis, review, editing and revising the manuscript. AFAA Conceptualization, reviewed the manuscript and supervision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hassan Abol-Enein.

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Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Informed consent was taken from all patients. Approval was granted by Local Institutional Review Board approval (Sci-Ch-M-2021–86).

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Tarabay, H.H., Abol-Enein, H., Awadalla, A. et al. Gene expression and oxidative stress markers profile associated with toxic metals in patients with renal cell carcinoma. Mol Biol Rep 49, 1161–1169 (2022). https://doi.org/10.1007/s11033-021-06944-3

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