RESUMO
Background: Arf GTPase-activating proteins are aberrantly expressed in a variety of tumors, but their role in clear cell renal cell carcinoma (ccRCC) was unclear. Exploring the biological role of Arf GAP with GTP binding protein like domain, Ankyrin repeat and PH domain 2 (AGAP2) in ccRCC could improve our understanding on the aggressiveness and immune relevance of ccRCC. Methods: The expression of AGAP2 was analyzed based on the Cancer Genome Atlas (TCGA) database and verified in ccRCC samples using immunohistochemistry. The association between AGAP2 and clinical cancer stages was explored by TCGA dataset and UALCAN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to analyze the biological functions of AGAP2-related genes. Moreover, the relationship between AGAP2 and immune cell infiltration was investigated with TIME and TCGA dataset. Results: Compared to normal tissues, AGAP2 was upregulated in ccRCC tissues. Higher expression of AGAP2 was associated with clinical cancer stages, TNM stages, pathologic stages, and status. Prognostic analysis on AGAP2 showed that AGAP2 overexpression was associated with KIRC overall survival (OS) reduction (P = 0.019). However, higher expression of AGAP2 may improve the OS of CESC (P = 0.002), THYM (P = 0.006) and UCEC (P = 0.049). GO and KEGG analysis showed that AGAP2-related genes was related to T cell activation, immune activity and PD-L1 expression and PD-1 checkpoint pathway. Furthermore, our study showed that AGAP2 were significantly associated with T cells, Cytotoxic cells, Treg, Th1 cells, CD8 T cells, T helper cells. And AGAP2 expression level affected the abundance of immune cells infiltration. The infiltrating level of immune cells was different between the AGAP2 high-expression and low-expression groups. Conclusion: The expression of AGAP2 in ccRCC was higher than that in normal kidney tissues. It was significantly associated with clinical stage, poor prognosis, and immune cell infiltration. Therefore, AGAP2 may become an important component for ccRCC patients who receive precision cancer therapy and may be a promising prognostic biomarker.
RESUMO
To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p < .001) and B12 (256.0 versus 337.5; p < .001) levels, and higher median HCY (11.4 versus 7.95; p < .001) levels, and these differences seemed to be more pronounced in the younger participants (age < 35 yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p < .001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p < .001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA ≤ 8.84 and HCY ≥ 10.35 were the best cut-off values for ED diagnosis. Both FA (r = -0.703, p < .001) and B12 (r = -0.576, p < .001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.
