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The metastasis-associated gene MTA3, a component of the Mi-2/NuRD transcriptional repression complex, predicts prognosis of gastroesophageal junction adenocarcinoma.

Dong H, Guo H, Xie L, Wang G, Zhong X, Khoury T, Tan D, Zhang H - PLoS ONE (2013)

Bottom Line: The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer.MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential.Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China.

ABSTRACT
Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.

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Survival curves of patients according to expression statues of MTA3.(A) The OS was significantly better among the patients with MTA3-positive tumors than among the patients with MTA3-negative tumors (P<0.001). (B) Among the patients with no lymph node metastasis (N0), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.018). (C) Among the patients with lymph node metastasis (N1), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.003). (D) The OS among the patients with MTA3-negative/Snail-positive/E-cadherin-negative tumors was significantly worse than among the patients whose had tumors exhibited other expression patterns (P = 0.003).
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pone-0062986-g003: Survival curves of patients according to expression statues of MTA3.(A) The OS was significantly better among the patients with MTA3-positive tumors than among the patients with MTA3-negative tumors (P<0.001). (B) Among the patients with no lymph node metastasis (N0), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.018). (C) Among the patients with lymph node metastasis (N1), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.003). (D) The OS among the patients with MTA3-negative/Snail-positive/E-cadherin-negative tumors was significantly worse than among the patients whose had tumors exhibited other expression patterns (P = 0.003).

Mentions: To evaluate the prognostic impacts of MTA3-pathway components on the outcomes of patients with GEJ adenocarcinoma, we performed Kaplan-Meier survival analyses. The OS rate of patients with tumors that expressed MTA3 was significantly higher than that of patients with tumors that did not express MTA3 (P<0.001; Figure 3A). An analysis of the relationship between MTA3 expression and OS was performed separately in patients with lymph node metastasis (N1) and in patients without lymph node metastasis (N0). In both groups, the OS rate was higher in patients with tumors that expressed MTA3 than in patients with tumors that did not express MTA3 (P = 0.018 for N0 and P = 0.003 for N1; Figure 3B and 3C). In subgroup of patients with MTA3-negative/Snail-positive/E-cadherin-negative tumors, the OS rate was lower than in patients who had tumors with other expression patterns (P = 0.003; Figure 3D). Thus, the analysis indicates that expression of MTA3-pathway components is strongly associated with the survival of GEJ adenocarcinoma patients.


The metastasis-associated gene MTA3, a component of the Mi-2/NuRD transcriptional repression complex, predicts prognosis of gastroesophageal junction adenocarcinoma.

Dong H, Guo H, Xie L, Wang G, Zhong X, Khoury T, Tan D, Zhang H - PLoS ONE (2013)

Survival curves of patients according to expression statues of MTA3.(A) The OS was significantly better among the patients with MTA3-positive tumors than among the patients with MTA3-negative tumors (P<0.001). (B) Among the patients with no lymph node metastasis (N0), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.018). (C) Among the patients with lymph node metastasis (N1), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.003). (D) The OS among the patients with MTA3-negative/Snail-positive/E-cadherin-negative tumors was significantly worse than among the patients whose had tumors exhibited other expression patterns (P = 0.003).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643958&req=5

pone-0062986-g003: Survival curves of patients according to expression statues of MTA3.(A) The OS was significantly better among the patients with MTA3-positive tumors than among the patients with MTA3-negative tumors (P<0.001). (B) Among the patients with no lymph node metastasis (N0), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.018). (C) Among the patients with lymph node metastasis (N1), the OS was significantly better in the patients with MTA3-positive tumors than in the patients with MTA3-negative tumors (P = 0.003). (D) The OS among the patients with MTA3-negative/Snail-positive/E-cadherin-negative tumors was significantly worse than among the patients whose had tumors exhibited other expression patterns (P = 0.003).
Mentions: To evaluate the prognostic impacts of MTA3-pathway components on the outcomes of patients with GEJ adenocarcinoma, we performed Kaplan-Meier survival analyses. The OS rate of patients with tumors that expressed MTA3 was significantly higher than that of patients with tumors that did not express MTA3 (P<0.001; Figure 3A). An analysis of the relationship between MTA3 expression and OS was performed separately in patients with lymph node metastasis (N1) and in patients without lymph node metastasis (N0). In both groups, the OS rate was higher in patients with tumors that expressed MTA3 than in patients with tumors that did not express MTA3 (P = 0.018 for N0 and P = 0.003 for N1; Figure 3B and 3C). In subgroup of patients with MTA3-negative/Snail-positive/E-cadherin-negative tumors, the OS rate was lower than in patients who had tumors with other expression patterns (P = 0.003; Figure 3D). Thus, the analysis indicates that expression of MTA3-pathway components is strongly associated with the survival of GEJ adenocarcinoma patients.

Bottom Line: The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer.MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential.Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China.

ABSTRACT
Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.

Show MeSH
Related in: MedlinePlus