High expression of GRB14 is associated with cancer progression and poor prognosis in gastric cancer.

BACKGROUND

Growth factor receptor-bound protein 14 (GRB14) has emerged as a significant regulator in cancer progression and prognosis across certain cancer types. Nevertheless, its role in gastric cancer (GC) remain poorly characterized.

METHODS

We conducted a comprehensive investigation of GRB14 in GC, integrating bioinformatics analysis with experimental validation. The prognostic significance and functional profile of GRB14 was evaluated through survival analysis and GSEA. Additionally, we analyzed the variations in immune cell infiltration and responses to immunotherapy between groups with low and high expression levels of GRB14. To confirm GRB14 expression in GC tissues, we utilized RT-qPCR, western blot and immunohistochemistry (IHC) analysis. Subsequently, functional experiments were then employed to evaluate the functional role of GRB14 in GC cells.

RESULTS

Analysis of the TCGA_stomach adenocarcinoma (TCGA_STAD) cohort revealed notable GRB14 upregulation in GC tissues, which was subsequently validated through RT-qPCR, western blot and IHC analyses. Elevated GRB14 expression were found to correlate with poor clinical outcomes. GSEA results showed that the vitamin digestion and absorption, and retinol metabolism pathways were obviously inactivated in the high GRB14 expression group. Moreover, this group exhibited notably lower immune score, stromal score, ESTIMATE score, but higher tumor purity compared to the low GRB14 expression group. Meanwhile, patients in the high GRB14 expression group exhibited significant M2 macrophage infiltration and elevated TIDE scores, suggesting that high GRB14 expression may be linked to an immunosuppressive tumor microenvironment. Functional studies demonstrated that GRB14 deficiency remarkably reduced GC cell proliferation, migration and invasion, but induced cell apoptosis.

CONCLUSION

This evidence highlights that GRB14 may serve as a potential candidate for both prognostic evaluation and therapeutic intervention in GC.