Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis.
Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis.
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DOI：
10.1186/1741-7015-11-52
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发表时间：
2013-02-26
期刊：
影响因子：
9.3
通讯作者：
Martin RM
中科院分区：
文献类型：
--
作者：
Tan VY;Lewis SJ;Adams JC;Martin RM
Fasin-1是一种肌动蛋白捆绑蛋白，在许多人类肿瘤中都有表达，但在大多数正常上皮中都没有表达。Fasin-1促进癌细胞中丝状足突的形成、迁移和侵袭；在小鼠异种移植瘤模型中，它有助于转移。Fasin-1是侵袭性、转移性癌症的一个有趣的候选生物标记物，但来自人类肿瘤个人研究的数据尚未被系统地汇集。这项系统性审查是根据PRISMA指南进行的，酌情使用固定和随机效应模型进行荟萃分析。共有26项免疫组织化学研究对5种常见的人类癌症进行了荟萃分析。Fasin-1与乳腺癌(合并风险比HR=2.58；95%可信区间(CI)1.48~4.52；P=0.001)、结直肠癌(HR=1.6~1.86；P<；0.001)和食道癌(HR=1.35；CI 1.13~1.6；P=0.001)的死亡风险增加有关。在胃癌和肺癌中，没有证据表明Fascin-1与死亡率有关。Fasin-1与乳腺癌(HR=2.48；CI 1.38~4.46；P=0.002)和结直肠癌(HR=2.12；CI 1.00~4.47；P=0.05)进展的风险增加有关，与肺癌的进展无关(HR=0.95；CI 0.49~1.85；P=0.9)。Fasin-1与结直肠癌(合并风险比RR=1.47；CI1.26至1.71；P<；0.001)和胃癌(RR=1.43；CI1.21至1.70；P<；0.001)的淋巴结转移风险增加有关。尚无证据表明Fascin-1与肺癌或食道癌的淋巴转移有关。Fasin-1与结直肠癌(RR=1.70；CI1.18~2.45；P=0.004)和胃癌(RR=1.93；CI1.21~3.33；P=0.02)远处转移的风险增加有关。未观察到与食道癌远处转移有关。所有癌的合并提供了强有力的证据，表明Fascin-1与死亡(HR=1.44；CI 1.24至1.68；P<；0.001；n=3,645)、淋巴结转移(RR=1.36；CI 1.18至1.55；P<；0.001；n=2,906)和远处转移(1.76；1.34至2.32；P<；0.001；n=1,514)的风险增加有关。Fasin-1与乳腺癌、结直肠癌和食道癌的死亡风险增加以及结直肠癌和胃癌的转移风险一致相关。结果对各种敏感性分析是稳定的，不受预定义亚组的影响。这些数据将有助于合理决策，将Fascin-1作为生物标记物或治疗靶点的研究重点放在最相关的癌症上。
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. This systematic review was conducted in accordance with PRISMA guidelines, using fixed and random effects models, as appropriate, to undertake meta-analysis. 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). 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.
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