Amplification-Driven S100A11 Overexpression in Hepatocellular Carcinoma Is Associated with Metabolic Reprogramming, ECM Remodelling, and Immune Evasion: A Pan-Cancer Genomic Study

Abstract

Simple Summary S100A11, a calcium-binding S100 family protein, is increasingly implicated in carcinogenesis, yet its molecular regulation and clinical relevance across cancers remain unclear. Hepatocellular carcinoma (HCC) has poor prognosis, in part due to less effective patient stratification. In the present study, we integrated genomic, epigenetic, and transcriptomic data to characterise S100A11 alterations in HCC and assess their association with patient survival, with the aim of defining its potential as a diagnostic and prognostic biomarker. Increase in S100A11 copy number emerged as the dominant mechanism of dysregulation, inversely associated with methylation changes in the gene. Analysis of co-expressed genes associated S100A11 with metabolic reprogramming, extracellular matrix remodelling, and an immunosuppressive tumour microenvironment, while higher S100A11 expression was significantly associated with poor survival and correlated with more advanced tumour stage. These findings identify S100A11 as a candidate prognostic marker in HCC and suggest new avenues for understanding its contribution to disease progression.