OR32-04 IGSF11 as a Tumour Suppressor and Potential Diagnostic and Prognostic Biomarker in Adrenocortical Carcinoma: Insights from Clinical and Functional Analyses

Disclosure: A. Hashmi: None. S. Sidhu: None. G. Hutvagner: None.

Background: Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited diagnostic and prognostic biomarkers and therapeutic options. Immunoglobulin Superfamily Member 11 (IGSF11), a cell adhesion molecule and known ligand of VISTA (V-domain Ig suppressor of T cell activation), has been associated with tumour progression in various cancers due to its role in inhibiting T-cell activation and promoting immune evasion. Elevated IGSF11 expression is linked to poor prognosis in gliomas, colorectal, and hepatocellular carcinomas. However, its role in ACC remains unexplored, and understanding its function could provide novel insights into ACC pathogenesis and treatment. Methods: Bioinformatic analyses were conducted using GTEx adrenal cortex and The Cancer Genome Atlas (TCGA)-ACC datasets to assess IGSF11 mRNA expression and its correlation with clinical outcomes. Quantitative RT-qPCR and ELISA assays were performed on H295R ACC cell lines transiently transfected with an IGSF11 expression plasmid. Cell proliferation was assessed using live-cell imaging and WST-8 assays. Additionally, IGSF11 protein levels were measured in tissue homogenates from normal adrenal cortex, adrenal adenoma, and ACC samples. Results: IGSF11 mRNA expression was significantly lower in ACC tissues compared to normal adrenal cortex (p < 0.001). Survival analysis demonstrated that reduced IGSF11 expression correlated with poorer patient outcomes, particularly in the aggressive COC3 TCGA-ACC cluster. In H295R cells, IGSF11 overexpression led to a marked increase in mRNA and protein levels (p < 0.0001) and significantly reduced cell proliferation (p < 0.005). ELISA assays confirmed significantly reduced IGSF11 protein levels in ACC tissues compared to benign and normal tissues (p < 0.0001). Comparative prognostic analysis across 32 TCGA cancer types highlighted a unique role for IGSF11 in ACC, with a hazard ratio of 0.22 (p = 0.00034), contrasting with its tumour-promoting role in other cancers. Conclusion: IGSF11 exhibits a tumour-suppressive role in ACC, contrasting its immune-inhibitory, tumour-promoting function in other malignancies. Its downregulation in ACC correlates with poorer survival outcomes, positioning it as a promising diagnostic and prognostic biomarker and potential therapeutic target. Restoring IGSF11 expression may offer new avenues for ACC treatment, emphasizing the need for further investigation into its tissue-specific functions and therapeutic potential.

Presentation: Monday, July 14, 2025