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

Abstract

Introduction: Fibroblast activation protein-alpha (FAP-alpha) 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-alpha 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-alpha 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-alpha 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-alpha 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-alpha expression have a higher risk of metastasis than those with a low FAP-alpha expression. These findings support the potential importance of FAP-alpha as a biomarker for cancer metastasis prediction.