Integrated biomarker mapping reveals differential expression of senescence profiles in IDH-wild-type glioblastoma recurrent versus primary tumors.
PMID 42089920 | DOI 10.1007/s00428-026-04541-y · Virchows Archiv : an international journal of pathology · 2026
Glioblastoma (GBM) remains a lethal malignancy characterized by therapeutic resistance and recurrence. Emerging evidence suggests that senescent niches may shape tumor progression, support tumor stemness, and modulate immune engagement. We integrated transcriptomic data from the Glioma Longitudinal Analysis Consortium (GLASS; 118 primary and 113 recurrent IDH-wildtype GBM samples) with protein-level analysis from an independent cohort of 37 GBM patients (25 primary, 12 recurrent), including 6 matched primary-recurrent pairs. Senescence-, stemness-, and immune-related pathways were assessed using single-sample gene set enrichment analysis (ssGSEA), while immunohistochemistry quantified the expression of Lamin B1, Ki67, p53, SOX2, HLA-DRA, B2M, and CD56. Transcript-level validation was performed using matched-pair Wilcoxon testing in 101 GLASS pairs. Recurrent tumors demonstrated increased enrichment of senescence-associated transcriptional programs, including upregulated KAMMINGA_SENESCENCE and reduced TANG_SENESCENCE_TP53_TARGETS_DN scores. Lamin B1 and Ki67 protein levels were significantly lower in recurrent tumors (p = 0.004 and p = 0.016), while p53 expression increased overall (p = 0.001), suggestive of a senescence enrichment upon recurrence. In the matched analysis (6 pairs; 12 samples total), Lamin B1 and Ki67 generally trended lower at recurrence, although paired differences were not statistically significant. SOX2 expression remained broadly stable at the protein level but showed a modest decrease in RNA expression. Immune markers (HLA-DRA, B2M, CD56) exhibited minimal differences, although HLA-DRA increased significantly overall at recurrence (p = 0.025). Matched transcriptomic analysis in GLASS pairs supported recurrent-specific reductions in LMNB1, MKI67, and SOX2, with no consistent changes in TP53, HLA-DRA, B2M, or NCAM1. Recurrent IDH-wildtype GBM exhibits a transcriptional and protein expression shift towards a senescence-associated state with no concomitant changes in SOX2 and select immune markers.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | SOX2 | “Senescence-, stemness-, and immune-related pathways were assessed using single-sample gene set enrichment analysis (ssGSEA), while immunohistochemistry quantified the expression of Lamin B1, Ki67, p53, SOX2, HLA-DRA, B2M, and CD56.” | 0.98 | hgnc_dict_v1 |
| gene | HLA-DRA | “Senescence-, stemness-, and immune-related pathways were assessed using single-sample gene set enrichment analysis (ssGSEA), while immunohistochemistry quantified the expression of Lamin B1, Ki67, p53, SOX2, HLA-DRA, B2M, and CD56.” | 0.98 | hgnc_dict_v1 |
| gene | B2M | “Senescence-, stemness-, and immune-related pathways were assessed using single-sample gene set enrichment analysis (ssGSEA), while immunohistochemistry quantified the expression of Lamin B1, Ki67, p53, SOX2, HLA-DRA, B2M, and CD56.” | 0.98 | hgnc_dict_v1 |
| gene | LMNB1 | “Matched transcriptomic analysis in GLASS pairs supported recurrent-specific reductions in LMNB1, MKI67, and SOX2, with no consistent changes in TP53, HLA-DRA, B2M, or NCAM1.” | 0.98 | hgnc_dict_v1 |
| gene | MKI67 | “Matched transcriptomic analysis in GLASS pairs supported recurrent-specific reductions in LMNB1, MKI67, and SOX2, with no consistent changes in TP53, HLA-DRA, B2M, or NCAM1.” | 0.98 | hgnc_dict_v1 |
| gene | TP53 | “Matched transcriptomic analysis in GLASS pairs supported recurrent-specific reductions in LMNB1, MKI67, and SOX2, with no consistent changes in TP53, HLA-DRA, B2M, or NCAM1.” | 0.98 | hgnc_dict_v1 |
| gene | NCAM1 | “Matched transcriptomic analysis in GLASS pairs supported recurrent-specific reductions in LMNB1, MKI67, and SOX2, with no consistent changes in TP53, HLA-DRA, B2M, or NCAM1.” | 0.98 | hgnc_dict_v1 |
| population | Population | “We integrated transcriptomic data from the Glioma Longitudinal Analysis Consortium (GLASS; 118 primary and 113 recurrent IDH-wildtype GBM samples) with protein-level analysis from an independent cohort of 37 GBM patients (25 primary, 12 recurrent), including 6 matched primary-recurrent pairs.” | 0.80 | saudi_context_rules_v1 |