Association of future cancer metastases with fibroblast activation protein-α: a systematic review and meta-analysis

Introduction: Fibroblast activation protein-α (FAP-α) is a vital surface marker of cancer-associated fibroblasts, and its high expression is associated with a higher tumor grade and metastasis. A systematic review and a meta-analysis were performed to associate future metastasis with FAP-α expression in cancer.

Methods: In our meta-analysis, relevant studies published before 20 February 2024 were systematically searched through online databases that included PubMed, Scopus, and Web of Science. The association between FAP-α expression and metastasis, including distant metastasis, lymph node metastasis, blood vessel invasion, vascular invasion, and neural invasion, was evaluated. A pooled odds ratio (OR) with 95% confidence intervals (CI) was reported as the measure of association.

Results: A total of 28meta-analysis. The random-effects model for five parameters showed that a high FAP-α expression was associated with blood vessel invasion (OR: 3.04, 95% CI: 1.54-5.99, I ² = 63%, P = 0.001), lymphovascular invasion (OR: 3.56, 95% CI: 2.14-5.93, I ² = 0.00%, P < 0.001), lymph node metastasis (OR: 2.73, 95% CI: 1.96-3.81, I ² = 65%, P < 0.001), and distant metastasis (OR: 2.59; 95% CI: 1.16-5.79, I ² = 81%, P < 0.001). However, our analysis showed no statistically significant association between high FAP-α expression and neural invasion (OR: 1.57, 95% CI: 0.84-2.93, I ² = 38%, P = 0.161).

Conclusions: This meta-analysis indicated that cancer cells with a high FAP-α expression have a higher risk of metastasis than those with a low FAP-α expression. These findings support the potential importance of FAP-α as a biomarker for cancer metastasis prediction.