Fascin-1 is an actin-bundling
protein expressed in many human
carcinomas, although absent from most normal epithelia. Fascin-1 promotes filopodia formation, migration and invasion in
carcinoma cells; in mouse xenograft
tumor models it contributes to
metastasis. Fascin-1 is an interesting candidate
biomarker for aggressive, metastatic
carcinomas but data from individual studies of human
tumors have not yet been pooled systematically.
METHODS: This systematic review was conducted in accordance with
PRISMA guidelines, using fixed and random effects models, as appropriate, to undertake meta-analysis.
RESULTS: A total of 26 immunohistochemical studies of 5 prevalent human
carcinomas were identified for meta-analysis. Fascin-1 was associated with increased risk of mortality for breast (pooled hazard ratio, (HR) = 2.58; 95% confidence interval (CI) 1.48 to 4.52; P = 0.001), colorectal (HR = 1.60 (1.37 to 1.86; P <0.001) and esophageal
carcinomas (HR = 1.35; CI 1.13 to 1.60; P = 0.001). There was no evidence of association of
fascin-1 with mortality in gastric and lung
carcinomas.
Fascin-1 was associated with increased risk of
disease progression in breast (HR = 2.48; CI 1.38 to 4.46; P = 0.002) and
colorectal carcinomas (HR = 2.12; CI 1.00 to 4.47; P = 0.05), but not with progression of lung
carcinomas (HR = 0.95; CI 0.49 to 1.85; P = 0.9).
Fascin-1 was associated with increased risk of
lymph node metastasis in colorectal (pooled risk ratio (RR) = 1.47; CI 1.26 to 1.71; P <0.001) and gastric
carcinomas (RR = 1.43; CI 1.21 to 1.70; P <0.001). There was no evidence of association of
fascin-1 with
lymph node metastasis in lung or esophageal
carcinomas.
Fascin-1 was associated with increased risk of distant
metastasis in colorectal (RR = 1.70; CI 1.18 to 2.45; P = 0.004) and gastric
carcinomas (RR = 1.93; CI 1.21 to 3.33; P = 0.02). No association with distant
metastasis in esophageal
carcinomas was observed. Pooling across all the
carcinomas provided strong evidence for association of
fascin-1 with increased risk of mortality (HR = 1.44; CI 1.24 to 1.68; P <0.001; n = 3,645),
lymph node metastasis (RR = 1.36; CI 1.18 to 1.55; P <0.001; n = 2,906) and distant
metastasis (1.76; 1.34 to 2.32; P <0.001; n = 1,514).
CONCLUSIONS: Fascin-1 is associated consistently with increased risk of mortality in breast, colorectal and esophageal
carcinomas and with
metastasis in colorectal and gastric
carcinomas. The results were stable to various sensitivity analyses and did not vary by predefined subgroups. These data will assist rational decision making for focusing investigations of fascin-1 as a
biomarker or therapeutic target onto the most relevant
carcinomas.