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.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P< 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registered at Clinicaltrail.gov (NCT04952324).