Prognostic Significance of Pre-Intervention Circulating Cytokines in Digestive System Cancers: A Systematic Review and Meta-Analysis Publisher Pubmed

Summary: Can blood cytokines help forecast cancer outcomes? A meta-analysis links higher IL-6 and chemokines to poorer survival in some digestive cancers. #CancerBiomarkers #Oncology

Tajik F ; Rezagholizadeh F ; Razmi M ; Safaei S ; Alaeddini M ; Etemad Moghadam S ; Eini L
Source: Clinical and Translational Oncology Published:2026

Abstract

Background: Circulating cytokines can influence tumor progression and immune evasion, serving as non-invasive biomarkers in digestive system (DS) cancers. This study evaluates the prognostic significance of biofluid cytokines in DS cancers. Methods: Comprehensive literature search in various databases identified studies reporting the prognostic importance of serum or plasma cytokines based on multivariate data, focusing on overall survival (OS) and disease/relapse/progression-free/cancer-specific-survivals (DFS/RFS/PFS/CSS). Quality assessment was done using the Newcastle–Ottawa scale. Heterogeneity was evaluated through Chi-square-based Q and I2 analyses. Publication bias was assessed via funnel plots, Egger’s, Begg’s, and trim-and-fill methods, alongside subgroup and sensitivity analyses. Results: A total of 42 articles evaluating 7 blood cytokines in DS cancers were included, with IL-6 and the CXCL family being the most studied. Elevated IL-6 levels were significantly associated with poor survival outcomes in esophageal, hepatocellular, biliary tract, pancreatic, and colorectal cancers for both OS and DFS/RFS/PFS/CSS. High CXCL levels correlated with worse prognosis in colorectal (OS: HR = 2.019) and hepatocellular (OS: HR = 5.569, DFS/RFS/PFS/CSS: HR = 1.610) cancer patients. Higher CCL levels predicted poor OS (HR = 1.912) in colorectal cancer. Circulating IL-10, IL-1β, and TNF-α showed no significant correlation with survival outcomes in DS. Subgroup analyses revealed varying prognostic significances of each cytokine in different DS malignancies. Publication bias was minimal except for IL-6 in pancreatic carcinoma, affirming the robustness of most outcomes. Conclusion: Elevated circulating IL-6, CXCL, and CCL families may predict poor prognosis in certain DS, highlighting their potential as prognostic markers. Further studies are needed to translate these findings into clinical practice. PROSPERO registration number: CRD42022316733. © The Author(s), under exclusive licence to Federacion de Sociedades Espanolas de Oncologia (FESEO) 2026.