Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.
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ABSTRACT:
SUBMITTER: Shin NR
PROVIDER: S-EPMC3552976 | biostudies-literature | 2012 Nov
REPOSITORIES: biostudies-literature
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Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.
Shin Na Ri NR Jeong Eun Hui EH Choi Chang In CI Moon Hyun Jung HJ Kwon Chae Hwa CH Chu In Sun IS Kim Gwang Ha GH Jeon Tae Yong TY Kim Dae Hwan DH Lee Jae Hyuk JH Park Do Youn DY
BMC cancer 20121114
<h4>Background</h4>Epithelial-mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.<h4>Methods</h4>We examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail ...[more]
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Project description:Epithelial-mesenchymal transition (EMT) is in the highlights as a significant role in tumor progression and invasion. Snail was known as the one of regulators of EMT in various malignant tumors. The aim of this study was to investigate the effect of Snail on invasiveness/migratory ability of gastric cancer cell lines and clinicopathological and prognostic significance of Snail over-expression using immunohistochemistry in tissue microarray of 314 gastric adenocarcinomas (GC). Differential gene expression in Snail over-expressed GC was investigated using cDNA microarray analysis. Silencing of Snail by ShRNA induced decreased of invasion, migration of gastric cancer cell lines. In contrast, over-expression of Snail induced increased invasiveness and migratory ability of gastric cancer cell lines in accordance increase of VEGF and MMP11. Furthermore, the over-expression of Snail (≥75% nuclear staining of Snail) was significantly associated with tumor progression (p<0.0001), lymph node metastases (p=0.002), lymphovascular invasion (p=0.002), and perineural invasion (p=0.002) in 314 GC patient. Snail over-expression was also associated with poor prognosis (shorter survival) in GC patients (p=0.023). cDNA microarray revealed 213 differential expressed genes in Snail over-expressed GC tissues, including genes related to metastasis, invasion. Based on above results, it was suggested that Snail plays a significant role in invasiveness/migratory ability of GCs. In addition, Snail might be used to predictive biomarker for evaluation of prognosis or aggressiveness in GCs.
2012-05-18 | GSE38024 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is in the highlights as a significant role in tumor progression and invasion. Snail was known as the one of regulators of EMT in various malignant tumors. The aim of this study was to investigate the effect of Snail on invasiveness/migratory ability of gastric cancer cell lines and clinicopathological and prognostic significance of Snail over-expression using immunohistochemistry in tissue microarray of 314 gastric adenocarcinomas (GC). Differential gene expression in Snail over-expressed GC was investigated using cDNA microarray analysis. Silencing of Snail by ShRNA induced decreased of invasion, migration of gastric cancer cell lines. In contrast, over-expression of Snail induced increased invasiveness and migratory ability of gastric cancer cell lines in accordance increase of VEGF and MMP11. Furthermore, the over-expression of Snail (?75% nuclear staining of Snail) was significantly associated with tumor progression (p<0.0001), lymph node metastases (p=0.002), lymphovascular invasion (p=0.002), and perineural invasion (p=0.002) in 314 GC patient. Snail over-expression was also associated with poor prognosis (shorter survival) in GC patients (p=0.023). cDNA microarray revealed 213 differential expressed genes in Snail over-expressed GC tissues, including genes related to metastasis, invasion. Based on above results, it was suggested that Snail plays a significant role in invasiveness/migratory ability of GCs. In addition, Snail might be used to predictive biomarker for evaluation of prognosis or aggressiveness in GCs. 48 primary gastric adenocarcinoma fresh frozen tissues were used for microarray. All the tissues were obtained after curative resection after pathologic confirm at Pusan National University Hospital (PNUH, Busan, Korea) and Cheonnam University Hospital (CNUH, Cheonnam, Korea). Microarray experiment and data analysis were done at Cancer research institute, PNUH, Busan, Korea.
2012-05-17 | E-GEOD-38024 | biostudies-arrayexpress
Project description:ObjectiveTo investigate the value of Hypoxia-inducible factor 1 A (HIF1A) in predicting lymph node metastasis (LNM) stage and clinical outcomes of papillary thyroid cancer (PTC) patients.Materials and methodsThe HIF1A gene expression analysis in PTC was performed by bioinformatics approaches followed by evaluating its protein level using immunohistochemistry analysis. The role of HIF1A in predicting the LNM stage was evaluated by logistic regression analysis, nomogram construction, and receiver operating characteristic (ROC) analysis. We performed survival analyses to determine its prognostic value. Enrichment analysis was conducted, and immune cell infiltration and stromal content were evaluated to examine the underlying mechanism of HIF1A in PTC.ResultsHIF1A transcription and protein levels were significantly high in PTC tissue (P < 0.05). Its overexpression predicted high LNM risk and unfavorable prognosis for PTC patients (P < 0.05). Cox regression analysis revealed HIF1A as an independent prognostic biomarker for the disease-free interval (DFI) (P < 0.01). In addition, HIF1A was positively related to tumor-suppressive immunity but was negatively correlated with anti-tumor immunity. HIF1A upregulation was also associated with increased stromal content.ConclusionsHIF1A overexpression is an independent predictor for worse DFI in PTC. The HIF1A expression may affect the prognosis of PTC patients through immune- and stroma-related pathways. Our study provides new insight into the role of HIF1A in PTC biology and clinical management.
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Project description:BackgroundThe secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients.MethodsThe mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression.ResultsWe observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.ConclusionOur findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.
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Project description:BackgroundNotch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of osteosarcoma and its role and mechanism in osteosarcoma cells have never been reported.Materials and methodsIn this study, we performed a clinicopathological analysis of 70 cases of osteosarcoma, with primary focus on survival. Osteosarcoma cell lines MTH and U2OS were used. After knockdown of Notch3 by lentiviral transfection and siRNA, the cell cycle, cell viability, and wound healing capacity were assessed. Subsequently, the Transwell assay was performed, and the expression levels of hairy and enhancer of split-1 (Hes1) and matrix metalloproteinase 7 (MMP7) were detected by RT-PCR and Western blot assay. The expression of MMP7 was also detected after knockdown of Hes1. Animal experiments were performed by injecting the cell lines MTH of Notch3 knockdown into mice tail veins and comparing the development of lung metastasis with the control group.ResultsComparison of survival curves showed that Notch3 expression significantly impacts patient survival. Additionally, multivariate analysis revealed that Notch3 is an independent prognostic factor for osteosarcoma. In in vivo experiments, osteosarcoma-associated pulmonary metastasis in nude mice was reduced after Notch3 silencing. The expression of downstream effector molecule, Hes1, and that of the invasion and metastasis-associated proteolytic enzyme, MMP7, were reduced, and MMP7 was further decreased by Hes1 knockdown in in vitro experiments.ConclusionNotch3 is a prognostic factor for osteosarcoma and might regulate its invasion and metastasis through the downstream target gene Hes1 and effector MMP7.
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Project description:AimTo investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer.MethodsIn our previous study of human whole-genome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records.ResultsMR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stage I-IV carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043].ConclusionMR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.
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