Prognostic Significance of Tumor-Stroma Ratio in Hepatocellular and Gall Bladder Carcinoma: Protocol for a Systematic Review and Meta-analysis

Background: The tumor-stroma ratio (TSR) has emerged as a crucial prognostic marker in various cancers, including breast, colorectal, and lung cancers. However, evidence for its prognostic value in hepatocellular carcinoma (HCC) and gallbladder carcinoma (GBC) remains limited and inconsistent. This systematic review and meta-analysis will assess the prognostic significance of TSR in patients with HCC and GBC, determining its potential to guide clinical decision-making and improve patient outcomes. Methods: The PubMed, Scopus, and Web of Science databases will be comprehensively searched, with no language or publication date restrictions. Studies eligible for inclusion are cohort studies, and case-control studies, that evaluate the prognostic value of TSR in patients diagnosed with HCC or GBC. The TSR is defined as the proportion of stromal tissue relative to tumor cells, with a cut-off value of 50% used to categorize patients as TSR-high or TSR-low. Data extraction and quality assessment will be independently performed by three researchers, with extracted data including study details, patient demographics, and outcomes (overall survival). The quality of each study will be assessed using the Newcastle Ottawa Scale. Results: The results will be pooled in a meta-analysis, calculating hazard ratios (HR) for survival outcomes. Statistical heterogeneity will be assessed using the I², Q test, tau², and prediction intervals. Subgroup analyses and meta-regression will explore potential sources of heterogeneity, and sensitivity analyses will be conducted to test the robustness of the findings. Publication bias will be evaluated using Begg’s funnel plot and Egger’s test. Conclusion: This study will evaluate the prognostic significance of TSR in hepatocellular carcinoma and gallbladder carcinoma.