AUTHOR=Facundo AN , Magalhães M , Nascimento GC , Azulay RS , Santos RM , Freitas LA , Nascimento AGPAC , Rodrigues VP , Santos WC , Beckman AMGS , Abreu JMF , Silva RP , Carneiro EL , Oliveira Neto CP , Gil da Costa RM , Corcoy R , Mato E , Faria MS 

TITLE=The expression of VDACs and Bcl2 family genes in pituitary adenomas: clinical correlations and postsurgical outcomes

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1481050

DOI=10.3389/fendo.2024.1481050

ISSN=1664-2392

ABSTRACT=<sec><title>Introduction</title><p>Pituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis.</p></sec><sec><title>Objective</title><p>to evaluate the gene expression of <italic>VDAC1, VDAC2, BAK1</italic> and <italic>BAX</italic> and their association with clinical and imaging characteristics in PA.</p></sec><sec><title>Methods</title><p>Clinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method.</p></sec><sec><title>Results</title><p>The sample was mainly composed of women (69/117 – 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 – 62.4%), Acromegaly (24/117 – 20.5%) and Cushing’s Disease (CD) (20/117 – 17.1%). Compared to normal tissue, there was a significant reduction in <italic>VDAC1</italic> expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. <italic>BAX</italic> expression was lower in all groups (p &lt;0.001; p=0.007; P =0.005). No difference was found in <italic>VDAC2</italic> and <italic>BAK1</italic> expression, compared to normal pituitary. Overexpression of <italic>VDAC2</italic> occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in <italic>BAX</italic> and <italic>BAK1</italic> expression in CD.</p></sec><sec><title>Conclusion</title><p>The results indicated that downregulations of <italic>VDAC1</italic> and <italic>BAX</italic> may be related to resistance to apoptosis. In contrast, overexpression of <italic>VDAC2</italic> in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs.</p></sec>