Fig. 4: LMNA expression is induced by TMZ and co-expressed with PRKDC in malignant glioblastoma cells, correlating with poor patient survival.

A Volcano plot from proteomic profiling. GBM6 and GBM6R cells treated with temozolomide (TMZ, 50 µM) or DMSO control were subjected to bottom-up proteomics via liquid chromatography–tandem mass spectrometry (LC-MS/MS), highlighting LMNA as significantly upregulated. B RNA sequencing analysis shows a significant increase in LMNA transcript levels following TMZ treatment in both GBM6 and GBM6R cells. C Immunoblot analysis confirms upregulation of LMNA protein in response to TMZ in both GBM6 and GBM6R cells. D Immunoprecipitation shows TMZ-induced LMNA–PRKDC complex formation. This assay reports interaction, not global DNA damage; lower input γH2AX in GBM6R reflects faster repair, not absence of engagement. E Time-course immunoblot analysis of patient-derived GBM43 and GBM5 cells reveals progressively increased LMNA expression following repeated TMZ treatments. F Single-cell transcriptomic analysis of GBmap dataset. (Top) UMAP clustering of LMNA⁺ (blue), PRKDC⁺ (green), and LMNA⁺/PRKDC⁺ (red) cells in non-malignant and malignant populations from the GBmap single-cell transcriptomic dataset. (Bottom) Dot plot summarizing the distribution of LMNA-only, PRKDC-only, double-positive, or double-negative cells across distinct malignant GBM cell types. G Kaplan–Meier survival analysis from the CGGA dataset, accessed via GlioVis, indicates significantly improved survival in patients with low LMNA expression in both primary and recurrent GBM cohorts.