ArticleBiomarker research2026
Soluble immune checkpoints as diagnostic biomarkers in bladder cancer.
Article in Biomarker research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Bladder cancer (BC) is a common malignancy with high recurrence and substantial monitoring costs. Limitations of current diagnostic tools: cystoscopy is invasive and expensive, urine cytology lacks sensitivity and existing urine biomarkers cannot replace cystoscopy, underscoring the need for improved non-invasive methods. Immune checkpoints (ICs) regulate immune activity, and newer ICs: T-cell immunoglobulin and mucin domain 3 (TIM-3), galectin-9 (Gal-9), B- and T-lymphocyte attenuator (BTLA), herpesvirus entry mediator (HVEM), cluster of differentiation 160 (CD160), and lymphocyte-activation gene 3 (LAG-3), are involved in cancer immune evasion. This study demonstrated that levels of soluble ICs (sICs) are markedly elevated in patients with early-stage BC. Serum levels of sTIM-3, sGal-9, sBTLA, sHVEM, sCD160, and sLAG-3 were quantified in BC and controls. sTIM-3, sGal-9, and sBTLA were significantly elevated in BC, while their concentrations didn’t vary by tumor stage or grade, supporting diagnostic rather than prognostic utility. Whereas sHVEM, sCD160, and sLAG-3 showed no diagnostic value. Age, sex, and body mass index (BMI) had minimal influence on sIC levels. Receiver operating characteristic (ROC) analyses showed strong performance: sGal-9 was the best classifier (area under the curve (AUC) = 0.98; 91% sensitivity; 100% specificity), followed by sTIM-3 (AUC = 0.91) and sBTLA (AUC = 0.78). sHVEM, sCD160, sLAG-3 performed poorly. A multivariate model incorporating sGal-9, sTIM-3, and sBTLA achieved a cross-validated AUC = 0.982, with sGal-9 remaining independently predictive. Correlation analyses revealed two clusters: sGal-9/sTIM-3/sBTLA and sHVEM/sCD160, that relationships align with known receptor-ligand biology and may reflect shedding during T-cell exhaustion. Overall, sGal-9, supported by sTIM-3 and sBTLA, constitutes promising serum biomarker panel associated with early-stage BC, however, as these markers are not disease-specific and may be affected by inflammatory or other pathological conditions, further validation is required.
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