Association of SMAD4 loss with drug resistance in clinical cancer patients: A systematic meta-analysis
Open Access
- 28 May 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (5), e0250634
- https://doi.org/10.1371/journal.pone.0250634
Abstract
Drug resistance frequently led to the failure of chemotherapy for malignant cancers, hence causing cancer relapse. Thus, understanding mechanism of drug resistance in cancer is vital to improve the treatment efficacy. Here, we aim to evaluate the association between SMAD4 expression and the drug resistance in cancers by performing a meta-analysis. Relevant studies detecting SMAD4 expression in cancer patients treated with chemo-drugs up till December 2020 were systematically searched in four common scientific databases using selected keywords. The pooled hazard ratio (HR) was the ratio of hazard rate between SMAD4neg population vs SMAD4pos population. The HRs and risk ratios (RRs) with 95% confidence intervals (CIs) were used to explore the association between SMAD4 expression losses with drug resistance in cancers. After an initial screening according to the inclusion and exclusion criteria, eleven studies were included in the meta-analysis. There were a total of 2092 patients from all the included studies in this analysis. Results obtained indicated that loss of SMAD4 expression was significantly correlated with drug resistance with pooled HRs (95% CI) of 1.23 (1.01–1.45), metastasis with pooled RRs (95% CI) of 1.10 (0.97–1.25) and recurrence with pooled RRs (95% CI) of 1.32 (1.06–1.64). In the subgroup analysis, cancer type, drug type, sample size and antibody brand did not affect the significance of association between loss of SMAD4 expression and drug resistance. In addition, there was no evidence of publication bias as suggested by Begg’s test. Findings from our meta-analysis demonstrated that loss of SMAD4 expression was correlated with drug resistance, metastasis and recurrence. Therefore, SMAD4 expression could be potentially used as a molecular marker for cancer resistance.This publication has 42 references indexed in Scilit:
- Genetically Defined Subsets of Human Pancreatic Cancer Show Unique In Vitro ChemosensitivityClinical Cancer Research, 2012
- Smad4 Inactivation Promotes Malignancy and Drug Resistance of Colon CancerCancer Research, 2011
- Phosphorylated Smad2 in Advanced Stage Gastric CarcinomaBMC Cancer, 2010
- Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analysesEuropean Journal of Epidemiology, 2010
- Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesisOncogene, 2009
- SMAD4 Gene Mutations Are Associated with Poor Prognosis in Pancreatic CancerClinical Cancer Research, 2009
- TGFβ in CancerCell, 2008
- Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progressionJCI Insight, 2008
- Practical methods for incorporating summary time-to-event data into meta-analysisTrials, 2007
- Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasisOncogene, 1999