CD44 family proteins in gastric cancer: a meta-analysis and narrative review

With a meta-analysis and narrative review, we evaluated the clinical and prognostic role of all CD44 family proteins in gastric cancer (GC). Literatures published up to August 2014 were searched on PubMed. Among the 37 eligible studies (6606 patients), 34 were included in meta-analysis, and 10 were subjected to narrative review. With meta-analysis, standard CD44 (CD44s) was demonstrated to predict reduced overall survival (OS) (HR = 1.93, 95% CI: 1.58-2.34, P-HR = 0.0222) and disease free survival (HR = 3.13, 95% CI: 1.02-9.68, P-HR = 0.0469), advanced N-stage (RR = 1.12, 95% CI: 1.04-1.21, P-RR = 0.0019), and distant metastasis (RR = 2.14, 95% CI: 1.46-3.14, P-RR < 0.0001) of GC. CD44 variant 6 (CD44v6) in GC might influence OS (5 studies; HR = 1.27, 95% CI: 0.75-2.14, P-HR = 0.3783; 4 studies; HR = 1.52, 95% CI: 1.09-2.14, P-HR = 0.0139), while significantly associated with N-stage (RR = 1.23, 95% CI: 1.03-1.48, P-RR = 0.0240), M-stage (RR = 2.54, 95% CI: 1.08-6.00, P-RR = 0.0333), TNM-stage (RR = 1.72, 95% CI: 1.18-2.50, P-RR = 0.0045), Lauren type (RR = 0.67, 95% CI: 0.50-0.91, P-RR = 0.0106), lymphatic invasion (RR = 1.13, 95% CI: 1.04-1.23, P-RR = 0.0057), and liver metastasis (RR = 3.20, 95% CI: 1.94-5.27, P-RR < 0.0001) of the disease. Moreover, a narrative review was performed for CD44 isoforms, such as v3, v5, v7, v8-10, and v9, in GC. In conclusion, CD44s and CD44v6 as evaluated by immunohistochemistry, respectively, predicts the prognosis and disease severity of GC.