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Wang X.-P.,Sun Yat Sen University | Li X.-H.,Sun Yat Sen University | Zhang L.,Sun Yat Sen University | Zhang L.,Guangdong Esophageal Cancer Institute | And 6 more authors.
BMC Cancer | Year: 2016

Background: Noninvasive prognostic tools for esophageal squamous cell carcinoma (ESCC) are urgently needed. Serum lipids and lipoproteins are used for the prognosis of certain diseases; however, the prognostic value of serum apolipoprotein A-I (ApoA-I) in ESCC has not been described. Methods: Pre-treatment serum lipids and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) were analyzed retrospectively and compared between 210 patients with ESCC and 219 healthy controls. The prognostic significance of serum lipids and lipoproteins was determined by univariate and multivariate Cox hazard models in ESCC. Results: Clinical characteristics (age, sex, pT status, pN status, pM status, pTNM status, histological differentiation or alcohol index) had no influence on baseline ApoA-I level. Serum ApoA-I, HDL-C, LDL-C, and TC levels were significantly lower and Apo-B was significantly higher in ESCC patients than in normal controls. On univariate analysis, ApoA-I, alcohol index, pT status, pN status and pTNM status were associated with significantly poor survival, and ApoA-I (p = 0.039), alcohol index (p = 0.037) and pTNM status (p = 0.000) were identified as prognostic factors associated with shorter survival in the multivariate analysis. Conclusions: Overall survival was shorter in ESCC patients with decreased pre-treatment ApoA-I levels. Our findings suggest that serum ApoA-I level should be evaluated as a predictor of survival in patients with ESCC. © 2016 Wang et al. Source

Zhu Y.-H.,Sun Yat Sen University | Zhang B.,Sun Yat Sen University | Li M.,Sun Yat Sen University | Huang P.,Sun Yat Sen University | And 5 more authors.
Diagnostic Pathology | Year: 2015

Background: Family with sequence similarity 3, member C (FAM3C) has been identified as a novel regulator in epithelial-mesenchymal transition (EMT) and metastatic progression. However, the role of FAM3C in esophageal squamous cell carcinoma (ESCC) remains unexplored. The purpose of present study is to illustrate the role of FAM3C in predicting outcomes of patients with ESCC. Methods: FAM3C expression was measured in ESCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR and Western blot analysis. The relationship between FAM3C expression and prognosis of ESCC patients was further evaluated by univariate and multivariate regression analyses. Univariate and multivariate analyses of the prognostic factors were performed using Cox proportional hazards model. Results: The FAM3C mRNA expression was remarkably upregulated in ESCC compared with their nontumor counterparts (P < 0.001). In addition, high expression of FAM3C was significantly associated with pT stage (P = 0.014) , pN stage (P = 0.026) and TNM stage (P = 0.003). Kaplan-Meier analysis showed that the 7-year overall survival rate in the group with high expression of FAM3C was poorer than that in low expression group (32.0 versus 70.9 %; P < 0.001). Univariate and multivariate analyses demonstrated that FAM3C was an independent risk factor for overall survival. Moreover, Stratified analysis revealed that FAM3C expression could differentiate the prognosis of patients in early clinical stage (TNM stage I-II). Conclusions:FAM3C expression was dramatically increased in ESCC and might serve as a valuable prognostic indicator for ESCC patients after surgery. © 2015 Zhu et al. 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 10 more authors.
Annals of Surgical Oncology | Year: 2015

Background: The correlation between vascular endothelial growth factor (VEGF) and prognosis for patients with esophageal squamous cell carcinoma (ESCC) is controversial. This study investigated the correlation of VEGF expression with distant metastases and prognosis in resectable ESCC to improve the identification of patients with increased risk of postoperative metastases. Methods: Data from two centers were used to establish a training cohort (n = 319) and a validation cohort (n = 164). Tissue microarrays were generated for immunohistochemical evaluation. The correlations among VEGF expression, clinicopathologic variables, and prognosis were analyzed. The outcomes generated from the training cohort then were tested using the validation cohort. Multivariate analyses were used to test the independent factors that had an impact on postoperative distant metastases, overall survival (OS), and distant metastasis-free survival (DMFS). Results: Tumor stages, tumor cell grade, and VEGF expression were prognostic factors independent of ESCC outcome. The data indicated that high levels of VEGF expression were correlated with a high risk of postoperative distant metastases (p = 0.013) in the training cohort. This result was confirmed by the validation cohort (p < 0.01) and logistic regression analyses. A high level of VEGF expression also was correlated with poor DMFS (p = 0.011) and OS (p = 0.033) in the training cohort, which also was confirmed by the validation cohort and Cox regression analyses. Conclusions: Expression of VEGF is a predictor of distant metastasis, OS, and DMFS in resectable ESCC patients. Using a combination of VEGF expression, tumor stages, and tumor cell grade, identification of patients with increased risk of postoperative metastases may become possible. © 2015, Society of Surgical Oncology. Source

Yang H.,Sun Yat Sen University | Yang H.,Guangdong Esophageal Cancer Institute | Li X.-d.,Sun Yat Sen University | Li X.-d.,Guangdong Esophageal Cancer Institute | And 10 more authors.
Oncotarget | Year: 2015

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P > 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC. Source

Zeng L.-S.,Sun Yat Sen University | Zeng L.-S.,Guangdong Esophageal Cancer Institute | Yang X.-Z.,Sun Yat Sen University | Yang X.-Z.,Guangdong Esophageal Cancer Institute | And 11 more authors.
Aging | Year: 2016

Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological function of HDAC4 in esophageal carcinoma (EC). We found that HDAC4 mRNA and protein are overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. Mechanistically, HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation. HDAC4 also enhances ESCC cell migration. Furthermore, HDAC4 positively regulates epithelial-mesenchymal transition (EMT) by increasing the expression of Vimentin and decreasing the expression of E-Cadherin/a-Catenin. Together, our study shows that HDAC4 overexpression is important for the oncogenesis of EC, which may serve as a useful prognostic biomarker and therapeutic target for this malignancy. Source

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