Integrated transcriptomic network analysis reveals shared immunogenomic regulators between glioma and type 2 diabetes, highlighting VCAN as a prominent marker

Abstract

Glioma patients with type 2 diabetes show heterogeneous clinical outcomes, yet the underlying immunogenomic connections remain poorly defined. We aimed to identify shared peripheral immune transcriptomic signatures linking glioma (GBM/LGG) and T2D. Using an integrated systems biology framework combining single-cell and bulk RNA-seq, gene co‑expression networks, and transcription factor-regulatory networks, we characterized convergent transcriptomic and regulatory alterations across the two conditions. Functional bioinformatic analyses and qPCR validation further examined key candidate markers. A set of shared immune-related genes and their regulators was identified between glioma subtypes (GBM and LGG) and T2D, among which VCAN, SATB1, and CEBPD emerged as top candidates. These markers were associated with inflammatory processes and monocyte trafficking signatures. Notably, VCAN emerged as a consistently significant marker in both GBM and T2D across multiple bioinformatic analyses and qPCR validation. Overall, this study highlights candidate immunogenomic regulators linking peripheral immune alterations in glioma and T2D and provides a framework for future mechanistic studies on metabolic-immune interactions in cancers.