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Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis.

ABSTRACT: 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.

SUBMITTER: Tan VY

PROVIDER: S-EPMC3635876 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis.

Tan Vanessa Y VY Lewis Sarah J SJ Adams Josephine C JC Martin Richard M RM

BMC medicine 20130226

<h4>Background</h4>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.<h4>Methods</h4>This systematic review was co ...[more]

PMID: 23442983

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Project description:Background: Previous studies have suggested that serum total bilirubin (STB) levels are associated with heightened chronic kidney disease (CKD) and mortality in both the general population and nephropathy patients. However, these results remain inconsistent. The aim of our study was to investigate whether STB was a predictor for progression of CKD and mortality by meta-analysis. Methods: We performed a systematic literature search in PubMed, Web of Science, MEDLINE, EMBASE, Google Scholar, and Cochrane Library's database up to June 30, 2019. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) were extracted for the highest vs. lowest category STB levels within the physiological range, and a random-effects model was applied to calculate the dose-response relationships. A pooled hazard ratio (HR) was used to investigate the association between STB levels and mortality in dialysis patients. Results: A total of 16 studies, wherein participants were followed from 21 months to 7 years, were eligible for inclusion in the study. For the categorized STB, 11 studies with 41,188 participants were identified and analyzed. Patients with the highest STB levels were associated with a lower risk of CKD (RR = 0.64; 95% CI 0.55-0.73) compared to those with the lowest STB levels. Furthermore, based on seven studies, a pooled RR of 0.89, 95% CI (0.80-0.99) was observed for the continuous STB levels (per 0.2 mg/dL increase). Four studies that included 51,764 participants illustrated that there was no association between STB levels and all-cause mortality (HR = 0.77; 95% CI 0.42-1.41). A prominent negative linear relationship (X2 = 14.70; P = 0.0001) was found between STB levels and risk of CKD. Subgroup analyses showed that there were no significant differences in the subgroup adjustment factor except for sample size. Conclusions: Elevated STB levels within a physiological range are associated with lower risk of CKD regardless of the study characteristics and coincide with a liner dose-response relationship. However, whether high STB levels are a protective factor against mortality remains inconclusive. Large-scale randomized controlled trails are needed to target STB levels for predicting renal outcomes.

Project description:Objectives To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality.Design Meta-analysis of prospective cohort studies.Data sources Electronic databases (PubMed, Embase, and Google Scholar).Selection criteria Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes.Review methods Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol : (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals.Results 53 prospective cohort studies with 1 611 339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality.Conclusions Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol.

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Dataset Information

Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis.

Publications

Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis.

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