Overexpression of S100 Calcium-Binding Protein A2 is Associated With Poor Prognosis in Hepatocellular Carcinoma

IntroductionS100 calcium-binding protein A2 (S100A2) is associated with various tumors. However, its expression profile, clinical relevance, and prognostic value in hepatocellular carcinoma (HCC) remain unclear; therefore, this study assessed S100A2 expression levels in HCC and adjacent normal tissues.MethodsTo investigate the role of S100A2 in HCC, RNA sequencing and DNA methylation data were obtained from The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC) cohort comprising 374 tumor and 50 normal liver tissues. A retrospective cohort of 216 HCC patients was also evaluated for correlations between S100A2 expression and clinicopathological characteristics. In a subset of 62 paired tumor and adjacent normal tissues, S100A2 protein and mRNA levels were assessed by immunohistochemistry (IHC) and quantitative RT-PCR. Finally, the relationship between S100A2 overexpression and clinicopathological variables was examined using the Cox proportional hazards regression model.ResultsAnalysis of the TCGA-LIHC dataset revealed a marked elevation in S100A2 expression in tumor tissues compared to normal liver tissues. Consistently, DNA methylation analysis showed hypomethylation of several S100A2-associated CpG sites in liver hepatocellular carcinoma, suggesting a potential epigenetic mechanism for its upregulation. Correlation analysis demonstrated that increased S100A2 expression was associated with advanced histological grade, lymph node metastasis, serum alpha-fetoprotein level, microvascular invasion, tyrosine kinase inhibitor level, concurrent treatment, and higher Tumor, Node, Metastasis stage. Univariate analysis showed that elevated S100A2 levels were associated with significantly poorer recurrence-free survival (RFS) and overall survival (OS). Moreover, multivariate analysis identified S100A2 as an independent prognostic indicator for both RFS and OS. Kaplan-Meier survival curves also confirmed that patients with high S100A2 protein levels had significantly worse 5-year OS and RFS rates.ConclusionThese findings indicate that S100A2 overexpression is associated with poor prognosis in patients with HCC, highlighting its potential utility as a diagnostic biomarker.