DIFFERENTIAL EXPRESSION OF PROLIFERATION AND SENESCENCE MARKERS IN RECURRENT GLIOBLASTOMA: INSIGHTS FROM MULTI-DATASET ANALYSIS

Abstract AIMS This study aimed to elucidate the roles of therapy-induced senescence (TIS), cancer stemness, and immune eva- sion in glioblastoma (GBM) recurrence by analyzing molecular and immune marker dynamics between paired primary and recurrent tumors. METHODS Integrated analysis of gene expression datasets (GSE62153, GSE79671, TCGA, CGGA) and immunohistochemistry (IHC) on paired primary/recurrent GBM samples was conducted. Evaluated markers included TIS (LMNB1, TP53, MKI67), stemness (SOX2), and immune regulation (HLA-DRA, B2M, NCAM1). Statistical significance was assessed using t-tests or non-parametric equivalents. RESULTS In GSE62153, TP53 and SOX2 were elevated in primary tumors (12/15 and 10/15 samples, respectively), though nonsignificant. NCAM1 (CD56) was significantly upregulated in relapsed tumors (12/15, p=0.02). Post-treatment analysis (GSE79671) revealed TP53 downregulation (p=0.037) and reduced SOX2 (9/11 samples), with elevated pretreatment B2M (p=0.039). TCGA identified significant SOX2 (p=0.004) and NCAM1 (p=0.003) increases in re- currence; CGGA showed upregulated MHC-I/II (B2M: p=7.33E-05; HLA-DRA: p=0.001). IHC confirmed higher nu- clear p53 (48.33% vs. 42.63%, p=0.042), higher Ki67 (22.56% vs. 14.42%, p=0.038) in recurrent tumors and compa- rable Lamin B1 expression between primary (64.21%) and recurrent tumors (69.44%, p = 0.552928). Alongside reduced CD56 (57.22% vs. 76.76%, p=0.033). SOX2 and HLA-DRA exhibited higher protein levels in primary GBMs (80.5% vs 75% and 27.9% vs 36.3%, respectively) but was not significant. B2M declined in recurrent tu- mour (42.9% vs 37.8%, p= 0.48). CONCLUSION Recurrent GBM exhibits heightened proliferation (elevated Ki67/p53), variable TIS profiles, and altered immune dynamics, including reduced CD56. While stemness markers (SOX2) decline post-treatment, MHC-I/II upregu- lation in specific cohorts highlights immune heterogeneity. These findings underscore the complexity of GBM recurrence, driven by evolving molecular interactions between senescence, stemness, and immune evasion. Future studies must dissect these mechanisms to inform therapeutic strategies targeting recurrence.