Background: Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no effective therapeutic target, intra- and intertumoral heterogeneity, inadequate effective drugs, and an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas and finding out the working mechanisms are urgent and necessary for glioma treatment. Identification of prognostic biomarkers and targeting the biomarker genes will be a promising therapy. Methods: From our RNA-sequencing data of the oxidative phosphorylation (OXPHOS)-inhibition sensitive and OXPHOS-resistant cell lines, we found that the scaffolding protein caveolin 1 (CAV1) is highly expressed in the resistant group but not in the sensitive group. By comprehensive analysis of our RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) data and public databases, we found that CAV1 is highly expressed in gliomas and its expression is positively related with pathological processes, higher CAV1 predicts shorter overall survival. Results: Further analysis indicated that (1) the differentiated genes in CAV1-high groups are enriched in immune infiltration and immune response; (2) CAV1 is positively correlated with tumor metastasis markers; (3) the methylation level of CAV1 promoters in glioma group is lower in higher stage than that in lower stage; (4) CAV1 is positively correlated with glioma stemness; (5) higher expression of CAV1 renders the glioma cells’ resistant to oxidative phosphorylation inhibitors. Conclusion: Therefore, we identified a key gene CAV1 and deciphered its function in glioma progression and prognosis, proposing that CAV1 may be a therapeutic target for gliomas. Graphical

Background Tertiary lymphoid structures (TLS) are immune niches linked to antitumor responses. Whether neural-like programs spatially associate with TLS in gastric cancer (GC) is unclear. Methods We integrated scRNA-seq (GSE183904), Visium spatial transcriptomics (GSE251950), and TCGA-STAD RNA-seq. A 15-gene neural-like (Neuro) program and TLS program were evaluated by Spearman correlation, Lee’s L, and a ReLU-corrected coupling score. Ligand–receptor co-expression and supportive CellChat domain inference were assessed; GSE245704 provided limited corroboration. Results Neuro activity localized mainly to fibroblasts and was driven by neural adhesion/glial markers. Unadjusted Neuro–TLS associations were positive (Spearman rho 0.143–0.559; Lee’s L 0.038–0.317; permutation p ≤ 0.006), but adjustment for microenvironmental components attenuated both measures and reversed their direction in a minority of sections, indicating partial composition dependence. NeuroHigh/TLSHigh domains had higher exhaustion-signature scores (p = 0.002). GSE245704 showed a directionally concordant association (rho = 0.193; Lee’s L = 0.109). In TCGA-STAD, Coupling_ReLU was associated with inferior overall survival after adjustment (HR = 1.291, 95% CI 1.062–1.569; p = 0.010); however, Neuro alone was significant (HR = 1.322; p = 0.001), suggesting that the prognostic signal may be partly driven by the stromal neural-adhesion component. Conclusions A stromal neural-adhesion program co-localizes with TLS niches, but the relationship is partly composition-dependent. Ligand–receptor co-expression and CellChat provide supportive domain-level inference rather than direct cell–cell interaction. These findings are hypothesis-generating and require larger cohorts, higher-resolution spatial profiling, and functional validation.

Fibroblast growth factor receptor 2 (FGFR2) is an oncogenic driver and therapeutic target in gastric cancer, but bulk profiling cannot resolve its intratum