PROTEIN KINASE C ALPHA (PKCa) EXPRESSION AS A POTENTIAL MARKER IN THYROID CANCER

CAMPOS HAEDO MN; DÍAZ ALBUJA JA; DÍAZ FLAQUÉ MC; CAYROL F; DEBERNARDI MM; STERLE HA; PERONA M; JUVENAL GJ; CREMASCHI GA; ROSEMBLIT C

Buenos Aires

Congreso; REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FISIOLOGÍA. 2023; 2023

Argentinean Physiological Society and the Latin American Association of Physiological Sciences

IntroductionThyroid cancer (TC) is the most common endocrine cancer, and its global incidence has been rising in recent decades. While many studies have linked PKCα overexpression to cancer aggressiveness and resistance to therapy, its specific role in TC remains underexplored. Objectives To assess if PKCα overexpression promotes tumor growth and its association with clinical and tumor factors in TC patients.Methods In vitro assays were conducted using human TC cell lines to examine PKCα role in tumor proliferation. We assessed protein expression and activation by qPCR, western blot, and Cell Titer Blue assays. To downregulate PKCα expression, siRNA transfection was employed. We further investigated PKCα expression and prognostic significance in TC patients from the TCGA-PanCancer Atlas TC database through bioinformatics tools. R2 Genomics Analysis and Visualization Platform (http://r2.amc.nl) analyses were performed on the GSE126729 dataset; for analyses on the Kaplan-Meier plotter (https://kmplot.com/), cBioPortal (https://cbioportal.org/) and Metascape (https://metascape.org/) platforms, mRNA sequencing data from the PanCancer Atlas were used. These findings were subsequently validated in TC patients from the British Hospital of Buenos Aires by immunihistochemistry (IHC).Results PKC expression in human TC cell lines showed high protein and mRNA levels compared to normal cells. PKCα downregulation significantly reduced hormone-induced proliferation. Our results also revealed PKCα´s involvement in AKT and Erk phosphorylation. Analyzing PKC family expression using R2 revealed that PKCα expression was highest in TC and anaplastic TC patients. cBioPortal analysis indicated a positive correlation between PKCα and PI3K-AKT pathway. Metascape analysis showed activation of MAPK and PI3K pathways in samples with PKCα overexpression. In the Kaplan-Meier Plotter, higher PKCα expression was associated with poorer overall survival in TC. Additionally, IHC indicated increased PKCα expression in 30% of patients with papillary thyroid microcarcinoma.Conclusion Our results establish that PKCα overexpression confers an advantage on tumor growth in TC. Therefore, it could act as a prognostic biomarker or therapeutic target in this disease.