Inflammation and detection: Rethinking the biomarker landscape in gastric cancer

Table 1 Diagnostic and prognostic value of cytokines in gastric cancer

Cytokine	Change in GC vs control	Diagnostic performance	Therapeutic/prognostic notes		Ref.
IL-1β	Increased in GC	AUC = 0.7; sensitivity approximately 0.76, specificity approximately 0.43	Central in Helicobacter pylori-driven inflammation; blocking IL-1β (e.g., canakinumab) is feasible; associated with tumor invasiveness and poor prognosis		Ren et al[1], Sánchez-Zauco et al[5]
IL-6	Increased in GC	AUC = 0.72; meta analysis: Sensitivity 0.80, specificity 0.86, AUC = 0.90	Potent growth and survival factor via Janus kinase/signal transducer and activator of transcription 3; high IL-6 predicts worse survival and chemoresistance		Ren et al[1], Kai et al[9], Janiczek-Polewska et al[10], Wang et al[12], Laurino et al[14]
IL-8	Increased in GC	AUC = 0.78; evidence mixed (some studies report no difference)	Promotes angiogenesis/metastasis; IL-8/CXC chemokine receptor 1 and 2 inhibitors reverse platinum resistance in preclinical GC models; rising IL-8 after treatment predicts chemoresistance		Ren et al[1], Liu et al[13], Jiang et al[15], Limpakan Yamada et al[16]
IFN-γ	Increased in GC	AUC = 0.65 (below 0.7)	Key T-cell cytokine; might reflect immune activation rather than tumor presence; Sánchez-Zauco et al[5] found it up in early GC; role in immunotherapy contexts		Ren et al[1], Sánchez-Zauco et al[5]
Multi-cytokine panel (IL-1β + IL-6 + IFN-γ)	Increased in GC	AUC = 0.888	Best diagnostic performance; synergistic detection		Ren et al[1]

AUC: Area under the curve; GC: Gastric carcinoma; IFN-γ: Interferon-gamma; IL: Interleukin.

Table 2 Selected inflammation-related biomarkers in gastric cancer

Biomarker	Function (immune role)	Diagnostic (AUC, sens/spec)	Stage association	Therapy relevance	Ref.
IL-1β	Pro-inflammatory, fever response; promotes tumor inflammation	AUC > 0.7 for GC	Increased with higher T/N stage	Not specific	Ren et al[1], Sánchez-Zauco et al[5]
IL-6	Pro-inflammatory, growth factor; STAT3 activator	AUC > 0.7; specificity approximately 97%, sensitivity approximately 39%	Increased with T/N stage; Increased in metastasis	Drives cisplatin resistance; targetable by anti-IL-6R therapy	Ren et al[1], Sánchez-Zauco et al[5], Wang et al[12], Thong-Ngam et al[21]
IL-8 (CXCL8)	Chemokine, neutrophil attractant; angiogenesis	AUC > 0.7	Likely increased in advanced/invasive GC (Helicobacter pylori linked)	Promotes metastasis; CXC chemokine receptor 1 and 2 inhibitors in trials	Ren et al[1]
IFN-γ	Th1 cytokine, anti-tumor effector	Increased in GC	Data limited	Reflects T-cell response; immunotherapy marker	Ren et al[1], Sánchez-Zauco et al[5]
IL-10	Anti-inflammatory, immunosuppressive (Tregs)	Low diagnostic yield alone	Increased in advanced disease, poor prognosis	Immunosuppressive tumor microenvironment; high IL-10 may predict poor ICI response	Szaflarska et al[19]
IL-11	IL-6 family, gp130/STAT3 activator (epithelial mitogen)	Not established for screening	Increased tumor/mucosal expression with stage	Mediates chemoresistance; anti-IL-11Rα agents under study	Necula et al[20]
IL-18	IFN-γ–inducer, Th1 cytokine	Sensitivity approximately 52.2%, specificity approximately 83.3% at 40 pg/mL	Likely increased with tumor burden	May potentiate immunotherapy via IFN-γ; possible adjuvant target	Thong-Ngam et al[21]
IL-24 (melanoma differentiation-associated gene-7)	Tumor-suppressor cytokine, induces cancer apoptosis	Investigational	Declined in tumors (anti-tumor effects)	Gene therapy for radiosensitization (preclinical)	Mao et al[22]
MIG (CXCL9)	T-cell chemoattractant (IFN-inducible)	Not used diagnostically	Increased in advanced GC	May predict T-cell infiltration; synergizes with checkpoint blockade	Baj-Krzyworzeka et al[23]
Macrophage inflammatory protein-1β (C-C motif ligands 4)	Monocyte/T-cell chemoattractant	Not used diagnostically	Increased in GC vs control (stage-independent)	May reflect myeloid infiltration	Baj-Krzyworzeka et al[23]
SIL-2Rα (CD25)	Marker of T-cell activation/regulation	Measured as immune activation index	Increased in advanced disease (likely)	Elevated by Tregs; may guide IL-2 or ICI therapy	Muhammad et al[25], Nakata et al[26], Park et al[28]
IL-6 rs1800796 (gene)	Promoter SNP (G/C) affecting IL-6 Levels	Not diagnostic	Not staging, but risk factor	High-risk allele may inform surveillance	Wang et al[29], Wang et al[27]
IL-8 rs4073 (gene)	Promoter SNP (T/A) affecting IL-8 Levels	Not diagnostic	Risk variant in Asians	Carriers may benefit from chemokine-targeted approaches	Wang et al[29]

Function and performance data are drawn from clinical studies. AUC: Area under the curve; CXCL: C-X-C motif ligand; GC: Gastric carcinoma; ICI: Immune checkpoint inhibitor; IFN-γ: Interferon-gamma; IL: Interleukin; SNP: Single nucleotide polymorphism; STAT3: Signal transducer and activator of transcription 3.