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Differential expression profiling of onco and tumor-suppressor genes from major-signaling pathways in Wilms’ tumor

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Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Purpose

Wilms’ tumor is the most-frequent malignant-kidney tumor in children under 3–4 years of age and is caused by genetic alterations of oncogenes (OG) and tumor-suppressor genes (TG). Wilms’ tumor has been linked to many OG-&-TG. However, only WT1 has a proven role in the development of this embryonic-tumor.

Methods

The study investigates the level of mRNA expression of 16 OGs and 20 TGs involved in key-signaling pathways, including chromatin modification; RAS; APC; Cell Cycle/Apoptosis; Transcriptional Regulation; PI3K; NOTCH-&-HH; PI3K & RAS of 24-fresh Wilms’-tumor cases by capture-and-reporter probe Code-Sets chemistry, as CNVs in these pathway genes have been reported.

Results

Upon extensively investigating, MEN1, MLL2, MLL3, PBRM1, PRDM1, SMARCB1, SETD2, WT1, PTPN11, KRAS, HRAS, NF1, APC, RB1, FUBP1, BCOR, U2AF1, PIK3CA, PTEN, EBXW7, SMO, ALK, CBL, EP300-and-GATA1 were found to be significantly up-regulated in 58.34, 62.5, 79.17, 91.67, 58, 66.66,54, 58.34, 66.67, 75, 62.5, 62.5, 58, 79.17, 79.17, 75, 70.84, 50, 50, 75, 66.66, 62.50, 61.66, 58.34-and-62.50% of cases respectively, whereas BRAF, NF2, CDH1, BCL2, FGFR3, ERBB2, MET, RET, EGFR-and-GATA2 were significantly down regulated in 58, 87.50, 79.16, 54.16, 79.17, 91.66, 66.66, 58.33, 91.66-and-62.50% of cases, respectively. Interestingly, the WT1 gene was five-fold down regulated in 41.66% of cases only.

Conclusion

Hence, extensive profiling of OGs and TGs association of major-signaling pathways in Wilms’ tumor cases may aid in disease diagnosis. PBRM1 (up-regulated in 91.67% of cases), ERBB2 and EGFR (down-regulated in 91.66 and 91.66% of cases, respectively) could be marker genes. However, validation of all relevant results in a larger number of samples is required.

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Data availability

Data sharing not applicable to this study as no datasets were generated or analyzed during the current study.

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Acknowledgements

This work was supported by SCIENCE AND ENGINEERING RESEARCH BOARD (SERB), National Post-Doctoral Fellowship award, file no. PDF/2016/001782, Government of India. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. We are very grateful to King George’s Medical University to facilitating the work. We are grateful to Miss. Archana Mishra, Dr. Pratap Pathak and Mr. NAwazish Alam for his technical assistance.

Funding

This work was supported by SCIENCE AND ENGINEERING RESEARCH BOARD (SERB), National Post-Doctoral Fellowship award, file no. PDF/2016/001782, Government of India. Dr Dinesh Kumar Sahu has received research grants from SERB, National Post-Doctoral Fellowship award, file no. PDF/2016/001782, Government of India. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Financial interests

The authors have no relevant financial or non-financial interests to disclose.

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Author notes

  1. Dinesh Kumar Sahu and Neetu Singh equally contributed to this work.

Authors and Affiliations

  1. Molecular Biology Unit, Center for Advance Research, King George’s Medical University, Lucknow, India

    Dinesh Kumar Sahu & Neetu Singh

  2. Postgraduate Institute of Child Health, Noida, India

    Dinesh Kumar Sahu

  3. Regional Medical Research Centre, Bhubaneswar, India

    Mumani Das

  4. Department of Paediatric Surgery, King George’s Medical University, Lucknow, India

    Jiledar Rawat

  5. Department of Paediatric Surgery, Post Graduate Institute of Child Health, Noida, India

    Devendra Kumar Gupta

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  1. Dinesh Kumar Sahu
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  2. Neetu Singh
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Contributions

Conceptualization: DKS; NS; Methodology: DKS; Formal analysis and investigation: DKS; Writing—original draft preparation: DKS; MD; Writing—review and editing: MD; DKG; Funding acquisition: DKS; Resources: NS; JR; Supervision: NS; DKG; JR.

Corresponding authors

Correspondence to Dinesh Kumar Sahu or Neetu Singh.

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Conflict of interest

Dr Dinesh Kumar Sahu has received research grants from SERB, National Post-Doctoral Fellowship award, file no. PDF/2016/001782, Government of India. All co-authors, who have contributed to the work and agreed to submit the manuscripts to this journal. This manuscript has not been previously published in any language anywhere and is not currently under consideration of publication by another journal. The authors also declare no conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Central Drugs Standard Control Organization (CDSCO), Government of India approved (Registration No; ECR/2621/Ins/UP/2013/RR/19) Institutional Ethics Committee of King George’s Medical University, Lucknow, India File no 1899/Ethics/2021 (Ref. Code: 85th ECM II A/P6). Written informed consent was obtained from the parents.

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Sahu, D.K., Singh, N., Das, M. et al. Differential expression profiling of onco and tumor-suppressor genes from major-signaling pathways in Wilms’ tumor. Pediatr Surg Int 38, 1601–1617 (2022). https://doi.org/10.1007/s00383-022-05202-2

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