Prognostic and clinicopathologic significance of FGFR mRNA and protein overexpression in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Fibroblast growth factor receptors (FGFRs), a family of receptor tyrosine kinases, regulate key cellular processes including proliferation, differentiation, and angiogenesis. Although dysregulated FGFR signaling has been implicated in cancer progression, the clinical significance of FGFR overexpression and its association with prognosis in CRC remain unclear, with inconsistent findings across FGFR subtypes, detection methods, and cutoff thresholds. Therefore, this meta-analysis aimed to systematically evaluate the association between FGFR protein/mRNA overexpression and prognosis and clinicopathological characteristics in CRC patients.

METHODS

Following the PRISMA guidelines, we searched PubMed, Web of Science, Embase, and the Cochrane Library from inception through March 12, 2026, for observational cohort studies evaluating the association between FGFR overexpression and survival outcomes in histologically confirmed CRC patients. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Primary outcomes were overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS); secondary outcomes included vascular invasion, lymph node metastasis, and distant metastasis. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed.

RESULTS

Thirteen studies involving 3,005 CRC patients were included, with a median NOS score of 7 (range, 5-8), indicating high methodological quality. FGFR overexpression was significantly associated with poorer OS (HR =1.95, 95% CI: 1.67-2.28) and DFS (HR =1.47, 95% CI: 1.05-2.07). Subgroup analyses showed that adverse prognostic associations were predominantly observed for FGFR2 (HR =2.79) and FGFR4 (HR =1.96) overexpression, whereas FGFR1 and FGFR3 overexpression showed no significant association with survival. Overall FGFR overexpression was significantly correlated with vascular invasion (OR =2.59, 95% CI: 1.12-5.97) but not with lymph node or distant metastasis.

CONCLUSIONS

The overall pooled analysis demonstrated that FGFR overexpression is significantly associated with poorer OS, DFS, and an increased risk of vascular invasion in CRC patients. Subgroup analyses further revealed that the adverse prognostic associations were particularly pronounced in cases of FGFR2 and FGFR4 overexpression, whereas FGFR1 and FGFR3 overexpression did not exhibit statistically significant associations with survival outcomes. These findings suggest that FGFR overexpression, especially involving specific FGFR subtypes, may represent a crucial molecular feature linked to CRC progression and prognosis. Further prospective studies are necessary to validate the prognostic relevance of FGFR subtype-specific overexpression and to explore its potential implications for individualized CRC management.