Table 2.
Key biomarkers in gastric cancer with their clinicopathological relevance, alterations, diagnosis, and targeted agents.
| Biomarker | Clinicopathological Relevance |
Activation Mechanism (Frequency, %) |
Detection Methods |
Representative Therapeutic Agents (Survival Benefit in Months *) |
Ref. |
|---|---|---|---|---|---|
| Established Biomarkers | |||||
| PD-L1 | EBV and MSI subtypeIncreased TILs (Inflamed phenotype) |
Overexpression (47–82%) |
IHC (membranous staining for tumor, membranous and/or cytoplasmic for immune cells) | Pembrolizumab (CPS ≥ 1; 0.8 months, CPS ≥ 10; 2.4 months) Nivolumab (all pts; 1.8 months, CPS ≥ 1; 2.7 months, CPS ≥ 5; 3.3 months) |
[7,8,9,10,11,12,13,14] |
| HER2 | Upper third of the stomach, CIN subtype, Intestinal type | Overexpression/Amplification (7–53%) | IHC (membranous staining) FISH, NGS |
Trastuzumab (all pts; 2.7 months, FISH +/IHC 2+ or IHC3+; 4.2 months) Trastuzumab deruxtecan (4.1 months)Trastuzumab + Pembrolizumab (NA) |
[15,16,17,18,19,20,21] |
| VEGFR2 | NA | Overexpression † (tumor cell; 0–54%, endothelial cell; ~50%) |
IHC † (nuclear, cytoplasmic, or membranous staining for tumor, cytoplasmic for endothelial cells) | Ramucirumab (2.2 months) |
[22,23,24,25] |
| Emerging Biomarkers | |||||
| MET | CIN subtype, Intestinal type Prognostic indicators of poor survival co-amplification in EGFR, HER2, and other RTK |
Overexpression (22–63%) Amplification (2–3%) Exon 14 skipping Mutation (~7%) |
IHC (membranous and/or cytoplasmic)FISH, NGS, ctDNA | AMG 337 (NA)Savolitinib (NA)Crizotinib (NA) | [26,27,28,29,30,31,32,33,34,35] |
| FGFR2 | GS (9%) > CIN (8%) Diffuse type > intestinal type Predictor for poor prognosisAssociated with lymphatic metastasis |
Overexpression (FGFR2b; 4%) Amplification (4–7%) |
IHC (membranous)FISH, NGS, ctDNA | Bemarituzumab (all pts; 5.7 months, FGFR2b ≥ 10%; 14.3 months) |
[36,37,38,39,40] |
| CLDN18.2 | GS subtype, Diffuse type, non-antral location, EBV positivityNo correlation with survival outcome | Overexpression (14–52%) |
IHC (membranous) | Zolbetuximab (all pts; 4.7 months, CLDN18.2 ≥ 70%; 7.6 months) |
[41,42,43,44,45] |
| TIL | EBV and MSI subtype | - | - | TIL therapy (NA) | [3,46,47,48,49] |
Abbreviations: EBV: Epstein—Barr virus; MSI: microsatellite instable; TIL: tumor-infiltrating lymphocyte; IHC: immunohistochemistry; CPS: combined positive score; CIN: chromosomal instability; FISH: fluorescence in situ hybridization; NGS: next-generation sequencing; NA: not applicable; RTK: receptor tyrosine kinase; ctDNA: circulating tumor DNA; GS: genomically stable. * Best survival benefit in months (prolonged median overall survival in targeted therapy group compared to control group) reported from the key clinical trials. † Not predictive for representative targeted drugs.