Gastric Cancer Biomarkers: From Cellular Identity to Precision Oncology

Gastric Cancer (GC) is characterized by remarkable biological heterogeneity, reflected by the continuous expansion of biomarkers with diagnostic, prognostic, predictive, and therapeutic relevance. However, most reviews organize these biomarkers according to signaling pathways or individual molecular alterations, often overlooking the interconnected biological processes and functional states that shape gastric carcinogenesis and tumor evolution. This review proposes a biology-oriented conceptual framework that interprets GC biomarkers through five fundamental biological questions capturing interconnected biological capabilities and tumor states: preservation of gastric lineage identity, acquisition of stem cell-like properties, epithelial-mesenchymal transition, immune evasion, and dependence on actionable oncogenic pathways. Within each biological domain, biomarkers were critically selected and comparatively evaluated according to their biological significance, pathological applicability, translational relevance, and clinical utility. Core biomarkers central to each biological process are discussed alongside complementary biomarkers that further refine biological interpretation and clinical stratification. Rather than presenting another comprehensive catalogue of molecular alterations, this review integrates current evidence into a coherent framework linking tumor biology with diagnostic pathology and precision oncology. By emphasizing biological capabilities rather than isolated molecular pathways, this approach provides a practical perspective for biomarker interpretation and establishes a conceptual foundation for future multimarker strategies in GC.