Clinical Significance and Expression Pattern of RIP5 and VGLL4 in Clear Cell Renal Cell Carcinoma Patients Treated with Sunitinib

Author:

Tomić Tanja1,Tomić Davor23,Vukoja Martina3,Kraljević Marija4,Ljevak Ivona1,Glamočlija Una5ORCID,Tomić Vajdana136ORCID,Vukojević Katarina137ORCID,Beljan Perak Renata8,Šoljić Violeta13

Affiliation:

1. Faculty of Health Studies, University of Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina

2. Department of Urology, University Hospital Center Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina

3. Laboratory of Morphology, Department of Histology and Embryology, School of Medicine, University of Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina

4. Department of Oncology, University Hospital Center Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina

5. Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina

6. Department of Gynecology, University Hospital Center Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina

7. Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia

8. Department of Pathology, Forensic Medicine and Cytology, University Hospital of Split, Spinčićeva 1, 21000 Split, Croatia

Abstract

While clear cell renal cell carcinoma (ccRCC) is curable, advanced metastatic (mRCC) remains a clinical challenge. We analyzed clinical, pathohistological, and molecular data (Receptor Interacting Protein 5—RIP5 and Vestigial Like Family Member 4—VGLL4 expression) of 55 mRCC patients treated with first-line treatment with sunitinib. The trend of linear increase in the protein expression of RIP5 was observed with the progression of tumor grade. Overall, 80% of RIP5-positive cells were in the control kidneys and high-grade mRCC. On the contrary, RIP5 displayed low expression in grade 2 mRCC (5.63%). The trend of linear decrease in the expression of VGLL4 was observed with the progression of tumor grade. The highest protein expression of VGLL4 was observed in grade 2 (87.82%) in comparison to grade 3 and 4 and control. High expression of RIP5 mRNA was associated with longer first-line overall survival and longer progression-free survival in mRCC. In addition, a high VGLL4 mRNA expression showed better overall survival in patients with ccRCC. In conclusion, high mRNA expression of RIP5 and VGLL4 are important markers of better survival rates in mRCC patients.

Funder

Faculty of Health Studies

Croatian Science Foundation

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Reference59 articles.

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3. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Sung;CA A Cancer J. Clin.,2021

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