Jiaqi Lao, Guangwei Tian, Lin Guan
Background: SARIFA (Stroma Areactive Invasion Front Areas) is an emerging histopathological biomarker defined by direct tumor-adipocyte contact at the invasive front. Preliminary studies suggest its association with poor prognosis, but evidence remains fragmented across cancer types. This meta-analysis aims to systematically evaluate the prognostic value of SARIFA for overall survival (OS) and its correlation with aggressive tumor phenotypes. Methods: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Cochrane up to December 2025. Studies reporting hazard ratios (HRs) for OS or odds ratios (ORs) for high-grade tumors related to SARIFA status were included. Data were pooled using Stata 12.0, and heterogeneity was assessed using I2 statistics. Subgroup, sensitivity, and publication bias analyses were performed. Results: Ten studies (6881 patients) showed that SARIFA positivity was significantly associated with worse OS (HR = 1.52, 95% CI: 1.42-1.63, I2 = 0.0%). Eleven studies (6847 patients) revealed that SARIFA positivity correlated with advanced tumor stage: pT (OR = 5.49), pN (OR = 2.80), pM (OR = 2.03), AJCC stage (OR = 4.04), and higher pathological grade (OR = 2.36). Heterogeneity was low for OS but substantial for pT (I2 = 87.4%), pM (I2 = 70.5%), and AJCC (I2 = 72.0%). Publication bias was absent for OS but present in pT- and AJCC-staging analyses. Trim-and-fill correction for pT indicated that statistical significance disappeared after imputing two missing studies (p changed from <0.001 to 0.450), suggesting that this association is not robust. Evidence for pancreatic and prostate cancers remains limited, each represented by only one study. Conclusions: SARIFA positivity is a strong predictor of poor overall survival and is significantly associated with aggressive tumor phenotypes, including advanced pT, pN, pM, AJCC stage, and higher pathological grade, supporting its potential as a practical prognostic biomarker in solid tumors.