Dataset Information

Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers.

ABSTRACT: Accumulating evidence indicates that Smad4 (DPC4) plays a fundamental role in the development and prognosis of several types of cancer. The objective of this study was to conduct a meta-analysis to evaluate whether the loss of Smad4 staining could serve as a prognostic marker.A comprehensive meta-analysis was conducted using major useful databases to determine the relationship between the immunohistochemical detection of Smad4 and the survival of patients with various cancers. We used hazard ratios (HRs) with 95% confidence interval (CIs) as the effect estimation to evaluate the association of Smad4 with overall survival (OS), cancer-specific survival (CSS) or recurrence-free survival (RFS). The relationship between the clinical characteristics of patients and Smad4 was also evaluated using the odds ratio (OR).A total of 7570 patients from 26 studies were included in the analysis. The pooled results showed that loss of Smad4 staining was a negative predictor of OS with an HR of 1.97 (95% CI: 1.55-2.51; Pheterogeneity<0.001) and CSS/RFS (HR?=?1.81; 95% CI: 1.30-2.54; Pheterogeneity<0.001). In addition, loss of Smad4 staining was more likely to be found in older (OR?=?1.69, 95% CI: 1.09-2.61; Pheterogeneity?=?0.648) colorectal cancer patients with a late tumor stage (OR?=?2.31, 95% CI: 1.71-3.10; Pheterogeneity?=?0.218) and in gastric cancer patients with lymph node metastasis (OR?=?2.11, 95% CI: 1.03-4.34; Pheterogeneity?=?0.038).Based on these results, our meta-analysis provided evidence that loss of Smad4 staining could act as an unfavorable biomarker in the prognosis of various cancers and should be used as a powerful tool in future clinical trials.

SUBMITTER: Du Y

PROVIDER: S-EPMC4198206 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers.

Du Yiping Y Zhou Xin X Huang Zebo Z Qiu Tianzhu T Wang Jian J Zhu Wei W Wang Tongshan T Liu Ping P

PloS one 20141015 10

<h4>Background</h4>Accumulating evidence indicates that Smad4 (DPC4) plays a fundamental role in the development and prognosis of several types of cancer. The objective of this study was to conduct a meta-analysis to evaluate whether the loss of Smad4 staining could serve as a prognostic marker.<h4>Methods</h4>A comprehensive meta-analysis was conducted using major useful databases to determine the relationship between the immunohistochemical detection of Smad4 and the survival of patients with ...[more]

PMID: 25333693

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Project description:BackgroundYes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. Many previous studies have explored the relationship between YAP1 and various types of cancer. However, these studies were limited by the small samples size and the findings were inconsistent among them. Therefore, a meta-analysis was conducted to assess the association between YAP1 and malignancies.MethodsA systematic literature search was conducted for eligible studies in the PubMed, Corchane Library, Web of Knowledge, EMBASE and CBM disc databases from inception to August 1st 2014. After heterogeneity analysis, pooled harzad ratio (HR) with 95% confidence interval (95%CI) using both fixed and random effect models were estimated in STATA 10.0. Meta regression analysis, subgroup analysis and sensitivity analysis were performed to explore the potential sources of heterogeneity and to evaluate the robustness of the result. Publication bias was assessed by Egger's test and funnel plot.ResultsA total of 21 unique articles from 2009 to 2014, comprising 2983 patients, were analyzed in the meta-analysis. The association of YAP1 expression and overall survival time (OS) was evaluated in 20 studies including 2067 patients. Positive YAP1 showed poorer OS (HR = 1.826; 95% CI = 1.465-2.275; p <0.002). For evaluating disease-free survival time (DFS), 10 studies with 1139 patients were analyzed. Positive YAP1 indicated worse DFS (HR = 2.114; 95%CI = 1.406-3.179; p <0.001). Subgroup analysis showed that both positive nuclear YAP1 (HR = 1.390, 95% CI: 0.810-2.400, p = 0.729) and up-regulation overall YAP1 (HR = 2.237, 95% CI: 1.548-3.232, p <0.001) had poorer OS for patients with malignancies. Similarly, both positive nuclear YAP1 (HR = 3.733, 95% CI: 1.469-9.483, p = 0.001) and up-regulation overall YAP1 (HR = 1.481, 95% CI: 1.163-1.886, p = 0.554) showed worse DFS. The patients with urogenital system cancer had the poorest OS (HR = 2.133, 95% CI: 1.549-2.937, p = 0.020). The patients with alimentary system cancer had the most significant impact on DFS (HR = 1.879, 95% CI: 1.537-2.297, p <0.001).ConclusionBoth overall and nuclear YAP1 overexpression are intimately associated with adverse OS and DFS in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future.

Dataset Information

Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers.

Publications

Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers.

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