Abstract
BackgroundAccumulating 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.MethodsA 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).ResultsA 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).ConclusionBased 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.
Highlights
For many years, cancer has been the leading cause of death worldwide, making it a global health problem [1]
Medical subheading (MeSH) terms related to Smad4 in combination with words related to cancer and terms related to prognosis were used to retrieve eligible studies through February 2014
Two articles evaluated the prognostic value for recurrence-free survival (RFS), and six evaluated the prognostic value for cancer-specific survival (CSS)
Summary
Cancer has been the leading cause of death worldwide, making it a global health problem [1]. Newer diagnostic methods to detect cancer with improved sensitivity and specificity have been developed. Because cancer is characterized by invasion and metastasis, which are the main factors contributing to its high mortality rate, the prognosis of cancer remains poor, with a disappointing five-year survival rate. Gastric, colorectal and pancreatic cancer, are common malignancies and are the leading cause of cancer-related deaths worldwide. Molecular prognostic biomarkers to predict the progression of the disease, response to treatment, and survival were widely explored during the past decades. Accumulating evidence indicates that Smad (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 Smad staining could serve as a prognostic marker
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