The clinical significance of snail protein expression in gastric cancer: a meta-analysis
© Chen et al. 2016
Published: 25 July 2016
Snail is a typical transcription factor that could induce epithelial-mesenchymal transition (EMT) and cancer progression. There are some related reports about the clinical significance of snail protein expression in gastric cancer. However, the published results were not completely consistent. This study was aimed to investigate snail expression and clinical significance in gastric cancer.
A systematic review of PubMed, CNKI, Weipu, and Wanfang database before March 2015 was conducted. We established an inclusion criterion according to subjects, method of detection, and results evaluation of snail protein. Meta-analysis was conducted using RevMan4.2 software. And merged odds ratio (OR) and 95 % CI (95 % confidence interval) were calculated. Also, forest plots and funnel plot were used to assess the potential of publication bias.
A total of 10 studies were recruited. The meta-analysis was conducted to evaluate the positive rate of snail protein expression. OR and 95 % CI for different groups were listed below: (1) gastric cancer and para-carcinoma tissue [OR = 6.15, 95 % CI (4.70, 8.05)]; (2) gastric cancer and normal gastric tissue [OR = 17.00, 95 % CI (10.08, 28.67)]; (3) non-lymph node metastasis and lymph node metastasis [OR = 0.40, 95 % CI (0.18, 0.93)]; (4) poor differentiated cancer, highly differentiated cancer, and moderate cancer [OR = 3.34, 95 % CI (2.22, 5.03)]; (5) clinical stage TI + TII and stage TIII + TIV [OR = 0.38, 95 % CI (0.23, 0.60)]; (6) superficial muscularis and deep muscularis [OR = 0.18, 95 % CI (0.11, 0.31)].
Our results indicated that the increase of snail protein expression may play an important role in the carcinogenesis, progression, and metastasis of gastric cancer. And this result might provide instruction for the diagnosis, therapy, and prognosis of gastric cancer.
Epithelial-mesenchymal transition (EMT), a developmental process whereby epithelial cells reduce intercellular adhesion and acquire myofibroblastic features, is critical to tumor progression [1–3]. Meanwhile, the dissolution of intercellular adhesions and the acquisition of a more motile mesenchymal phenotype as part of epithelial-to-mesenchymal transition (EMT) are crucial capacities of invading cancer cells . Snail can induce EMT partly by suppressing the expression of E-cadherin. Reduced expression of E-cadherin may lead to the loss of cell-cell adhesion and cancer progression . In recent years, snail was found to be highly expressed in several carcinomas, including non-small cell lung carcinomas, ovarian carcinomas, urothelial carcinomas, breast cancer, and hepatocellular carcinoma [6–10]. Studies of immunohistochemical analyses suggest that snail is highly expressed in gastric cancer and significantly associated with tumor progression and metastasis [11–13].
Study search protocol
A total of 10 studies were identified by primary search strategies using the keywords “snail” combined with “gastric cancer” and synonyms in PubMed, CNKI, Weipu, and Wanfang database.
Inclusion criteria and exclusion criteria
Studies that were included in this meta-analysis met the following criteria: (1) the official published literature or master’s and doctoral dissertation in both Chinese and English before March 2015; (2) the detection method used immunohistochemical and the results experienced quantitative analysis; (3) when duplicate articles were published, we included the newest or the most informative single study; (5) the snail positive rate was given or could be calculated based on the information from tables or figures.
Exclusion criteria included (1) repetitive studies; (2) research on animal and cellular level; (3) studies without reviews, letters, abstracts and editorials; and (4) the studies without control group.
Data extraction and quality assessment
Two reviewers screened the titles and abstracts according to the inclusion and exclusion criteria listed above independently. Then, they cross-checked the articles and removed disagreements. Information extracted from the eligible articles included first author, publication year, detection method, the number of cases and controls, the clinical pathology states of cases and controls, and the location of snail protein expression. The quality of these studies is assessed by the following: (1) whether the gold standard method is set up; (2) whether the gold standard test stayed is independent of the evaluation test; (3) whether the blind method is used; (4) whether quantitative data is given or is able to be calculated; (5) whether the definition and diagnosis of the case are correct, independent, and standard; (6) whether the diagnostic steps are detailed; (7) whether the case has a good representation; (8) whether cases and controls are selected and analyzed based on the most important factor. Based on the above standards, we classified the qualities of the research into five grades: (A) meets all 8 quality standards; (B) meets 7 standards; (C) meets 6 standards; (D) meets 5 standards; (E) meets 4 standards.
Meta-analysis was conducted with RevMan4.2 software. Odds ratio (OR) with 95 % confidence interval was calculated. Heterogeneity between studies was examined using the I2 statistic [14, 15]. When I2 value was greater than 50 %, we considered that heterogeneity was significant. Fixed-effect Mantel-Haenszel model was chosen as the main analysis method when the heterogeneities were not confirmed statistically significant. Otherwise, random-effect model was adopted. Funnel plots were used to check for the potential of publication bias. All the P values were two-sided, and statistically significant difference was defined as P < 0.05.
Literature search and study characteristics
Main characteristics of the studies included in this meta-analysis
Highly + moderate
TI + TII
TIII + TIV
The relationship between the expression of snail protein and the characteristics of clinical pathology
Publication bias analysis
Discussion and conclusions
This meta-analysis was aimed to examine the expression of transcription factor snail in different tissue samples and the relationship between increased snail expression and clinicopathological features of gastric cancer. This study combined 756 gastric cancer tissue samples, 346 para-carcinoma samples, and 171 normal tissue samples from 10 individual studies. The results indicated that snail expression is higher in gastric cancer tissues than that in para-carcinoma tissues and normal tissues, respectively (OR = 6.15, 95 % CI = 4.70, 8.05; OR = 17, 95 % CI = 10.08, 28.67). Furthermore, closed correlations were observed between snail expression and clinicopathological characteristics that included the lymph node metastasis, the degree of differentiation, TNM stage, and invasion depth. The positive expression rate of snail was higher in gastric cancer tissues with lymphatic metastasis, OR = 0.40, 95 % CI = (0.18, 0.93). The higher positive rate of snail is connected with the lower differentiation degree, OR = 3.34, 95 % CI = (2.22, 5.03). The positive expression of snail was higher at late clinical stage, OR = 0.38, 95 % CI = (0.23, 0.60). Moreover, it appeared that the deeper the infiltration was, the higher the expression of snail was, OR = 0.18, 95 % CI = (0.11, 0.31).
The result of funnel plot indicated an imminent possibility of publication bias. Two potential biases might be introduced. First, the languages in collected papers were used in both Chinese and English, which may lead to a language bias. Second, the majority of collected studies did not use blind method, which might result in a measurement bias. Hence, the large-scale samples and double blind statistical tests will be investigated in the future study. Additionally, our review only collected the publications that have full text, since data that can be used for the methodology assessment and meta-analysis were only available in these publications with full text.
Our meta-analysis indicated that snail was highly expressed in gastric cancer. In addition, the overexpression of snail is significantly associated with tumor progression and metastasis.
The research and publication of the research were supported by the Natural Science Foundation Hubei Province of China (2011CDB236 and 2012FFB04903).
This article has been published as part of Human Genomics Volume 10 Supplement 2, 2016: From genes to systems genomics: human genomics. The full contents of the supplement are available online at http://humgenomics.biomedcentral.com/articles/supplements/volume-10-supplement-2.
YC, YD, and JL envisioned the project. YC and LL designed the work. YC and LH constructed and validated the pathway models and performed the data analysis, with assistance from WY. YC, ZW, and HJ screened the data. YC, MY, WG, and HRA wrote the manuscript. YL polished the English. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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