Dataset Information

Prognostic and clinical significance of STAT3 and MMP9 in patients with gastric cancer: a meta-analysis of a Chinese cohort.

ABSTRACT: As signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascade directly contributes to tumor metastasis, numerous agents targeting STAT3 are in clinical development. However, reported data on the prognostic impact of STAT3 expression vary considerably. We aim to quantitatively summarize available evidences for evaluating the association between STAT3 and STAT3-regulated target gene, matrix metalloproteinase 9 (MMP9), and the prognosis of Chinese patients with gastric cancer. Searches were applied to PubMed and the Chinese National Knowledge Infrastructure database without any language restriction. A total of 5,757 patients were included in the final analyses. All results favored an association between high STAT3 expression and poor 5-year overall survival (risk ratio = 1.845, 95% confidence interval [CI] = 1.027-3.315). The reduced survival was heavily influenced by advanced tumor invasion (OR = 2.885, 95% CI = 2.034-4.094), lymph node metastasis (OR = 5.349, 95% CI = 3.807-7.516), distant metastasis (OR = 5.873, 95% CI = 2.641-13.062), dedifferentiation (OR = 2.516, 95% CI = 1.814-3.491), tumor size (OR = 1.918, 95% CI = 1.246-2.954), and higher TNM stage (OR = 4.171, 95% CI = 2.840-6.126). Similar results were observed in the meta-analyses of MMP9, with the magnitude of effect OR > 2. Our findings indicate that STAT3 and MMP9, as measured by IHC, are associated with worse survival and potentially mark invasion and metastasis in gastric cancer, especially in Chinese patients. More significantly, these two biomarkers may be converted from candidates to the routine clinical evaluation to help predict the outcome of gastric carcinoma patients.

SUBMITTER: Chen J

PROVIDER: S-EPMC4358484 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Prognostic and clinical significance of STAT3 and MMP9 in patients with gastric cancer: a meta-analysis of a Chinese cohort.

Chen Jing J Liu Xiaoxia X Jiao Haiyan H Peng Liang L Huo Zhenghao Z Yang Wenjun W Shen Qin Q Li Tao T Liu Qilun Q

International journal of clinical and experimental medicine 20150115 1

As signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascade directly contributes to tumor metastasis, numerous agents targeting STAT3 are in clinical development. However, reported data on the prognostic impact of STAT3 expression vary considerably. We aim to quantitatively summarize available evidences for evaluating the association between STAT3 and STAT3-regulated target gene, matrix metalloproteinase 9 (MMP9), and the prognosis of Chinese patients with gastric ca ...[more]

PMID: 25785029

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Project description:The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28-4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan-Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma.

Project description:PurposeThis study was to quantitatively summarize published data for evaluating the clinical and prognostic significance of four proteins involved in hypoxia-inducible factor-1 (HIF-1α) regulation of the metastasis cascade.MethodsSearches were performed using the MEDLINE, EMBASE, Cochrane Library, and Chinese Biomedicine databases without any language restrictions. Studies were pooled and either the summary risk ratio (RR) or odds ratio (OR) was calculated. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication bias was also performed.ResultsSeventeen studies evaluated HIF-1α, 20 studies evaluated phosphatase and tensin homolog (PTEN), 20 studies evaluated Survivin, and 16 studies evaluated CD44v6. Our results showed that increased HIF-1α expression was linked to a poor 5-year overall survival (RR = 1.508; 95% confidence interval (CI) 1.318-1.725; P<0.001). Decreased survival was heavily influenced by advanced tumor invasion (OR = 3.050; 95% CI 2.067-4.501; P<0.001), lymph node metastasis (1415 patients; OR = 3.486, 95% CI 2.737-4.440; P<0.001), distant metastasis (OR = 6.635; 95% CI 1.855-23.738; P = 0.004), vascular invasion (OR = 2.368; 95% CI 1.725-3.252; P<0.001), dedifferentiation (OR = 2.112; 95% CI 1.410-3.163; P<0.001), tumor size (OR = 1.921; 95% CI 1.395-2.647; P<0.001), and a higher TNM stage (OR = 2.762; 95% CI 1.941-3.942; P<0.001). Similarly, aberrant expression of PTEN, CD44v6, and Survivin were also observed in tumors that correlated with poor OS. The higher ORs of death at 5 years were 1.637 (95% CI = 1.452-1.845; P<0.001), 1.901 (95% CI = 1.432-2.525; P<0.001), and 1.627 (95% CI = 1.384-1.913; P<0.001), respectively, with an OR>2 for the main stratified meta-analyses of clinical factors.ConclusionsOur findings indicate that HIF-1α/PTEN/CD44v6/Survivin, as measured by immunohistochemistry, can be used to predict the prognosis and potential for invasion and metastasis in Asian patients with gastric cancer. The development of strategies against this subset of proteins could lead to new therapeutic approaches.

Project description:BackgroundAccurately distinguishing serosal invasion in patients with gastric cancer (GC) prior to surgery can be difficult. Molecular analysis of peritoneal fluid (MAPF) for free cancer cells with higher sensitivity than other methods; however, its prognostic value for GC remains controversial, precluding its application in clinical practice.MethodsPubMed, EMBASE and other databases were systematically searched. Thirty-one studies were eligible for the meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS) and peritoneal recurrence-free survival (PRF).ResultsThe current meta-analysis focused on patients with GC and negative cytological diagnoses. The results showed that positive MAPF status (MAPF+) led to poorer prognoses for OS (HR 2.59, 95% CI 1.99-3.37), DFS (HR 4.92, 95% CI 3.28-7.37) and PRF (HR 2.81, 95% CI 2.12-3.72) compared with negative MAPF status (MAPF-). Moreover, among the patients with GC who received curative treatment, the MAPF+ patients had poorer prognoses for OS (HR 3.27, 95% CI 2.49-4.29), DFS (HR 3.90, 95% CI 2.74-5.57) and PRF (HR 5.45, 95% CI 3.70-8.03). A meta-analysis of multivariate-adjusted HRs demonstrated that MAPF+ status was an independent prognostic factor for patients with GC who underwent curative treatment (OS: HR 2.19, 95% CI 1.47-3.28; PRF: HR 3.44, 95% CI 2.01-5.87). Using the identical target genes (CEA, CEA/CK20) as molecular markers, the patients with GC who were MAPF+ had significantly worse prognoses for OS (CEA: HR 3.03, 95% CI 2.29-4.01; CEA/CK20: HR 4.24, 95% CI 2.42-7.40), DFS (CEA: HR 3.99, 95% CI 2.24-7.12; CEA/CK20: HR 4.31, 95% CI 1.49-2.48) and PRF (CEA: HR 4.45, 95% CI 2.72-7.31; CEA/CK20: HR 6.46, 95% CI 3.62-11.55) than the patients who were MAPF-.Conclusion/significanceThe above results demonstrate that MAPF could be a prognostic indicator for patients with GC who have a negative cytological diagnosis and/or are receiving curative treatment. MAPF could provide clinicians with additional prognostic information that could aid in developing individualized treatment plans prior to surgery. The widely used target genes CEA, CEA/CK20 were confirmed to be valuable MAPF markers for predicting the prognosis of GC.

Project description:BackgroundTumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients.MethodsWe retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted.ResultsThe detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance.ConclusionsThe presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.

Dataset Information

Prognostic and clinical significance of STAT3 and MMP9 in patients with gastric cancer: a meta-analysis of a Chinese cohort.

Publications

Prognostic and clinical significance of STAT3 and MMP9 in patients with gastric cancer: a meta-analysis of a Chinese cohort.

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