Current Oncology
Nuclear Eccentricity as a Potential Biomarker for Tumor Biology and Survival in Glioblastoma
By Luna Han, Todd A. Perkins, Mohid Hassan and 1 others.
Abstract
Purpose
To investigate whether quantitative nuclear morphology from routine H&E images can be used as a biomarker for glioblastoma (GBM) biology and prognosis.
Methods
Nuclear eccentricity, circularity, density, and heterogeneity were measured from H&E whole-slide images in the TCGA-GBM cohort and independently validated in the CPTAC-GBM cohort. A multivariable Cox model was used to test the survival associations in both cohorts, and transcriptome-wide and gene set enrichment analyses were conducted in TCGA RNA data and validated using CPTAC RNA and proteomic data.
Results
In TCGA-GBM, greater nuclear eccentricity was associated with better survival (HR, 0.85; 95% CI, 0.71–1.02; p = 0.089), with the same favorable association independently observed in CPTAC-GBM (HR, 0.74; 95% CI, 0.60–0.90; p = 0.003). No individual gene association with eccentricity was statistically significant in the TCGA cohort, but pathway analysis identified its association with epithelial–mesenchymal transition (EMT), inflammatory, hypoxic, and stress-related programs. Across the TCGA RNA, CPTAC RNA and proteomic datasets, greater eccentricity was consistently associated with increased NF-κB signaling, collagen biosynthesis, and ER-to-Golgi transport and decreased L1CAM-related and neuronal-projection programs, with EMT showing the strongest cross-cohort consistency.