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Zhou S.L.,Zhengzhou University | Cui J.,Xinxiang Medical University | Fan Z.M.,Zhengzhou University | Li X.M.,Cixian Hospital | And 10 more authors.
BMC Cancer | Year: 2013

Background: The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA).Methods: We firstly analyzed the prevalence of RASSF1A A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the RASSF1A in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method.Results: The frequency of 133Ala/Se and Ser/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, P=0.02). Compared with Ala/Ala genotype, Ala/Se and Ser/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09-3.97). However, this polymorphism had no association with ESCC (P=0.69). The promoter methylation of RASSF1A gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78-12.52) and GCA (OR=7.50, 95% CI= 2.78-20.23). Promoter methylation of RASSF1A gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10-8.73; for differentiation: OR=0.29, 95% CI=0.12-0.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03-0.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57-167.74).Conclusions: The present findings suggest that alterations of RASSF1A may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, RASSF1A hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis. © 2013 Zhou et al.; licensee BioMed Central Ltd. Source


Yang H.-X.,Sun Yat Sen University | Yang H.-X.,State Key Laboratory of Oncology in South China | Wei J.-C.,Linzhou Esophageal Cancer Hospital | Xu Y.,Guangdong Pharmaceutical University | And 8 more authors.
Annals of Thoracic Surgery | Year: 2011

Background: More data are essential to test the efficacy of the American Joint Committee on Cancer (AJCC) system for staging esophageal squamous cell carcinoma. We tested the classifiers used in the AJCC staging system and propose a modification to this system to better represent the survival characteristics of esophageal squamous cell carcinoma in the Chinese population. Methods: We used data from two centers, which established the training (n = 1,006) and validation (n = 783) cohorts. All the patients underwent curative surgical treatment. Survival was compared using AJCC classifiers to test the efficacy of this staging system. Martingale residuals from a Cox proportional hazards regression model were used to modify the nodal categories. The results obtained from the training cohort were validated with the validation cohort at each step. Results: The evaluation of the patients' overall survival allowed only poor discrimination between AJCC IIIb and IIIc cancers in both cohorts. Also, in both cohorts, N2 and N3 classification cancers could not be well discriminated in terms of survival when AJCC nodal categories were used. Nevertheless, the survival rate could easily be distinguished when using the four modified categories: 0, 1, 2 to 3, and 4 or more positive nodes. The survival difference between IIIb and IIIc obtained using the modified nodal categories could easily be discriminated in both cohorts. Conclusions: Esophageal squamous cell carcinoma nodal staging for the Chinese population was more accurately classified using the following four categories: no positive node, 1 positive node, 2 to 3 positive nodes, and 4 or more positive nodes. Further studies are required to confirm these results. © 2011 The Society of Thoracic Surgeons. Source


Hou X.,Sun Yat Sen University | Hou X.,State Key Laboratory of Oncology in South China | Wei J.-C.,Linzhou Esophageal Cancer Hospital | Xu Y.,Guangdong Pharmaceutical University | And 10 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Controversy exists concerning the optimal cutoff points for the positive lymph node ratio (PLNR) to predict overall survival. We aim to propose reasonable PLNR categories for the discrimination of the survival difference between groups. Methods: We used data from two centers to establish a training (n = 1006) and a validation (n = 783) cohort. All of the patients underwent curative surgical treatment. Martingale residuals from a Cox proportional hazards regression model were used to determine the optimal cutoff points for PLNR to predict overall survival. The survival rate was calculated using the Kaplan-Meier method, and a log-rank test was used to assess the survival differences between groups. The results obtained from the training cohort were tested with the validation cohort at each step. Results: We classified the patients into four revised nodal categories: R-pN0 (PLNR = 0), R-pN1 (0< PLNR ≤0.1), R-pN2 (0.1< PLNR ≤0.3), and R-pN3 (PLNR >0.3). Subgroup analysis for the pT2 and pT3 cases showed that the survival differences could be well discriminated between groups based on PLNR in both the training cohort and validation cohort. When we modified the current staging system using revised nodal categories (based on PLNR) instead of the AJCC nodal categories, the survival rate could also be easily distinguished between patients in different stages in both cohorts of patients. Conclusions: The survival rate of ESCC can be discriminated between four groups: PLNR = 0, 0< PLNR ≤0.1, 0.1< PLNR ≤0.3, and PLNR >0.3. Further studies are required to confirm these results. © 2012 Society of Surgical Oncology. Source


Hou X.,Sun Yat Sen University | Liang R.-B.,Sun Yat Sen University | Liang R.-B.,Guangdong Esophageal Cancer Institute | Wei J.-C.,Linzhou Esophageal Cancer Hospital | And 10 more authors.
Oncotarget | Year: 2016

Purpose: We aim to identify esophageal squamous cell carcinoma patients with increased risk of postoperative metastases. Results: A high level of cyclin D1 expression, together with poor tumor cell differentiation and advanced tumor stages, increased risk of postoperative metastasis and decreased distant metastasis-free survival in ESCC in both cohorts. A high level of cyclin D1 expression also decreased overall survival in the training cohort (p < 0.01) but not in the validation cohort (p = 0.415). However, when the two cohorts of patients were pooled to obtain a larger case number, a high level of cyclin D1 expression was again demonstrated as an independent predictor that decreased overall survival (p < 0.01). Methods: We used data from two institutions to establish training (n = 319) and validation (n = 164) cohorts. Tissue microarrays were generated for immunohistochemical evaluation. The correlation among cyclin D1 expression, clinicopathologic variables, postoperative distant metastases, overall survival, and distant metastasis-free survival were analyzed. Multivariate analyses were used to test the independent factors impacting postoperative distant metastases and survival. The outcomes generated from the training cohort were then tested using the validation cohort and pooled dataset. Conclusions: High level of cyclin D1 expression increased distant metastasis, decreased overall survival and distant metastasis-free survival in resectable ESCC. Using a combination of cyclin D1 expression, tumor cell differentiation grade, and tumor stages, identifying patients with increased risk of postoperative metastases becomes possible. Source


Hou X.,Sun Yat Sen University | Hou X.,State Key Laboratory of Oncology in South China | Wei J.-C.,Linzhou Esophageal Cancer Hospital | Fu J.-H.,State Key Laboratory of Oncology in South China | And 9 more authors.
Annals of Surgical Oncology | Year: 2014

Background: More data are essential to test the efficacy of the American Joint Committee on Cancer (AJCC) system for staging esophageal squamous cell carcinoma (ESCC). On the basis of previous studies, we propose a modification to this system to better represent the survival characteristics of ESCC in the Chinese population. Methods: We used data from two centers to establish the generating (n = 1006) and validation (n = 783) cohorts. All of the patients underwent curative surgical treatment. On the basis of previous studies, we excluded tumor location as a variable in the modified pathological staging system and defined the modified nodal categories as follows: N0, node negative; N1, 1 positive node; N2, 2 to 3 positive nodes; and N3, >3 positive nodes. The pathological T categories, pathological M categories, and cell differentiation in the seventh AJCC staging system for adenocarcinoma were used in the modified pathological staging system for ESCC. Results: The median survival times for ESCC patients with stage 0 and Ia, stage Ib, stage IIa, stage IIb, stage IIIa, stage IIIb, stage IIIc were as follows: not reached, 221.2, 151.8, 88.5, 25.0, 19.0, and 13.0 months, respectively, for the entire cohort of patients (n = 1789). The corresponding 5-year survival rates were 86.7, 76.4, 64.9, 55.3, 29.9, 16.9, and 9.7 %, respectively. The survival rates significantly differed between the modified staging groups (p < 0.01). Conclusions: This modified staging system better discriminates the survival differences between stages than the seventh edition of the AJCC staging system for ESCC in Chinese patients. © 2013 Society of Surgical Oncology. Source

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