Prognostic significance of pre-intervention circulating cytokines in digestive system cancers: a systematic review and meta-analysis.

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.