Figure 3: Nuclear envelope rupture is associated with differences in lamin subtype expression in glioblastoma tissues.
A, Overview of 28-plex t-CyCIF experiment on a glioma tissue microarray (TMA). B, Selected t-CyCIF images of glioma TMA with cores de-arrayed. Right top: primary IDH-WT GBM tumor with high lamin A/C expression and few PN ruptures. Right bottom: primary IDH-WT GBM tumor with low lamin A/C expression and many PN ruptures. C,D, Examples of segmentation of PN rupture (C) and MN rupture (D). E,F, Probability density plots of lamin A/C, lamin B1, and lamin B2 protein expression in 161,834 PN (E) and 5,974 MN (F) from 82 primary IDH-WT GBM. P values as indicated (t-test, two-sided, unpaired). G,H, Scatter plot of the mean number of BAF foci per cell versus mean nuclear lamin A/C or lamin B1 expression in primary IDH-WT GBM (N=82, duplicate cores). Pearson correlation analysis shows that lamin A/C is inversely correlated with PN BAF focus frequency (rho=−0.28, p=0.02) (G); lamin B1 shows no significant association (rho=0.05, p=0.66) (H). I,J, t-CyCIF images of BAF, pH2AX, cGAS in primary IDH-WT GBM with PN (I) and MN (J) ruptures. K,L, Probability density plots of pH2AX (K) and cGAS (L) signal in segmented BAF+ rupture foci and BAF-negative PN. M,N, Probability density plots of pH2AX (M) and cGAS (N) signal in segmented BAF-positive PN and BAF-negative and -positive MN.
