The Association of SARIFA with Poor Prognosis and Aggressive Tumor Phenotypes in Cancers: A Meta-Analysis.

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.