Search

Background: This study investigated the expression and biological function of JAB1 in esophageal squamous cell carcinoma (ESCC). Methods: The expression of JAB1 in ESCC tissues and cells was measured using reverse transcriptase‐polymerase chain reaction (RT‐PCR), immunohistochemistry (IHC), and western blot analysis. Kaplan‐Meier survival analysis was performed to explore the effect of JAB1 expression on the prognosis of ESCC patients. Furthermore, experiments were conducted in vivo and in vitro to determine the effect of JAB1 expression on the malignant behavior of ESCC cells. Results: Compared with adjacent tissues, JAB1 was highly overexpressed in cancer tissues (P = 0.01). Univariate and multivariate analyses of clinical data indicated that patients with JAB1 overexpression had a worse prognosis (P = 0.001 and P = 0.049, respectively). Cell function experiments and tumorigenesis experiments in nude mice showed that the upregulation of JAB1 might promote malignant behavior, and vice versa. Conclusions: Overexpression of JAB1 promoted the proliferation, migration, and invasion of ESCC cells, and was significantly associated with poor prognosis of ESCC patients. Therefore, JAB1 could be considered as a promising prognostic factor and a possible target for the specific therapy of ESCC. Key points: In this study, we found that JAB1 was highly overexpressed in cancer tissues, which could influence the malignant behavior of ESCC cells, and was significantly associated with poor prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have elucidated that FOXM1 may predict poor prognosis in patients with multiple solid malignant tumors. In this study we explored the differential expression of FOXM1 in stage IIA esophageal squamous cell carcinoma (ESCC) and investigated its prognostic value. Methods: Immunohistochemistry (IHC) and Western blot were used to detect FOXM1 expression in ESCC. Correlations between FOXM1 expression and clinicopathological variables, and five‐year lymphatic metastatic recurrence (LMR) and overall survival (OS) of patients were analyzed. Results: FOXM1 was aberrantly expressed in ESCC. Statistical analysis revealed a close relationship between FOXM1 expression and tumor size (P = 0.024), depth of invasion (P = 0.048), and degree of differentiation (P = 0.043). The five‐year LMR of patients in the FOXM1 overexpression group was significantly increased compared to the low expression group (P = 0.001). The five‐year OS of patients in the FOXM1 overexpression group was significantly reduced compared to the low expression group (P = 0.007). Log‐rank tests demonstrated that large tumor size (P = 0.044), poor differentiation degree (P = 0.005), deep invasion (P = 0.000), and FOXM1 overexpression (P = 0.007) may indicate poor prognosis in stage IIA ESCC. Cox multivariate regression analysis revealed that all of these variables were independent predictors of unfavorable outcome (P < 0.05). Conclusion: FOXM1 could be a predictor of lymphatic metastatic recurrence in stage IIA ESCC after Ivor Lewis esophagectomy. [ABSTRACT FROM AUTHOR]

Background: Centrosomal protein 55 (CEP55) is an important prognostic biomarker that plays an essential role in the proliferation, migration and invasion of multiple tumors. We aimed to investigate the prognostic value of CEP55 in pN0 esophageal squamous cell carcinoma (ESCC) and explore its biological function in ESCC cells.Methods: We used immunohistochemistry and Western blot analysis to detect the expression of CEP55 in ESCC. Furthermore, both in vitro and in vivo assays were used to determine the effect of CEP55 on malignant behavior in ESCC cells.Results: As expected, we found that CEP55 was overexpressed in ESCC. Univariate and multivariate analyses demonstrated that patients with CEP55 overexpression had a poor prognosis. Additionally, the abilities of proliferation, migration and invasion of cells, as well as the epithelial–mesenchymal transition markers, were all altered with the changed CEP55 expression levels in ESCC cells. Further study elucidated that CEP55 facilitated ESCC via the PI3K/Akt pathway. Blockade of this pathway markedly attenuated CEP55-mediated proliferation, migration, invasion and epithelial–mesenchymal transition of ESCC cells.Conclusion: Oncogenic CEP55 correlates with a poor prognosis by regulating tumor cell proliferation, migration and invasion via the PI3K/Akt pathway. It can serve as a promising prognostic biomarker and therapeutic target of pN0 ESCC after Ivor-Lewis esophagectomy. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC), a type of non‑small cell lung carcinoma, has a poor therapeutic response, high relapse rate and poor prognosis. The present study was designed to reveal the key long non‑coding RNAs (lncRNAs) associated with the prognosis of LUSC. The lncRNA expression profiles of LUSC and adjacent samples were downloaded from The Cancer Genome Atlas database. Based on the edgeR and DEseq packages, the differentially expressed lncRNAs (DELs) between LUSC and adjacent samples were obtained and the intersecting DELs were regarded as significant DELs. Subsequently, a prognostic risk model was established using Cox regression analysis and its classification effect was detected by survival analysis. Using survival analysis, the effect of the prognostic risk model was assessed in the validation set and other types of cancer. Finally, the co‑expression genes of key lncRNAs were screened using the Multi‑Experiment Matrix tool and the STRING database, and their functions were predicted via enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery tool. A total of 2,041 significant DELs between LUSC and adjacent samples were screened. The prognostic risk model consisting of RP5‑821D11.7, APCDD1L‑AS1 and RP11‑277P12.9 was established, which had a good classification effect. Cox multivariate regression analysis demonstrated that risk score may serve as an independent prognostic factor. Furthermore, certain co‑expression genes of RP5‑821D11.7 (including proliferating cell nuclear antigen), APCDD1L‑AS1 (including semaphorin 5A, semaphorin 6D, ADAMTS like 1, ADAM metallopeptidase with thrombospondin type 1 motif 6, slit guidance ligand 3, and tenascin C) and RP11‑277P12.9 (including Wnt family member 2B) were identified. Additionally, ‘positive regulation of cell migration’ and ‘proteinaceous extracellular matrix’ were enriched. In conclusion, the expression levels of the lncRNAs RP5‑821D11.7, APCDD1L‑AS1 and RP11‑277P12.9 may affect the prognosis of LUSC. [ABSTRACT FROM AUTHOR]

Background Recent research has shown that IFITM3 plays an important role in the tumorigenesis of many malignancies. We investigated the clinicopathological variables and prognostic value of IFITM3 in stage IIA esophageal squamous cell carcinoma ( ESCC) patients. Methods Immunohistochemistry and Western blot analysis were used to examine IFITM3 expression in tumor specimens. The relationships between IFITM3 expression and clinicopathological variables, as well as the five-year survival and recurrence status of patients, were analyzed. Results IFITM 3 was aberrantly expressed in tumor tissue. Statistical analysis showed a close correlation of IFITM3 expression with T tumor status ( P = 0.004). Additionally, IFITM3 overexpression, advanced T status, poor degree of differentiation, and large tumor size were not only associated with poor survival but were high lymphatic metastatic recurrence predictors in ESCC patients ( P < 0.05). Conclusion Our data indicated that IFITM3 overexpression may predict poor prognosis in stage IIA ESCC patients after Ivor Lewis esophagectomy. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that Ku80 expression was implicated in development and progression of malignant tumors. In the present study, we analyzed for the first time the expression of Ku80 in locally advanced esophageal squamous cell carcinoma (ESCC) and its correlation with clinicopathologic features and patient survival. Methods: The expression profile of Ku80 was analyzed in 126 cases of locally advanced ESCC and 79 cases of normal subjects as control using immunohistochemistry and Western blot. The associations of Ku80 expression with clinicopathological features were estimated by χ test. We further performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) of patients. Results: Immunohistochemistry and Western blot analyses both showed the Ku80 protein expression was significantly higher in ESCC than normal esophageal mucosa and corresponding healthy esophageal mucosa. Statistical analysis suggested a significant correlation of Ku80 overexpression with the tumor size ( p = 0.037), differentiation degree ( p = 0.018), depth of invasion ( p = 0.020), lymph node metastasis ( p = 0.045), clinicopathological staging ( p = 0.001), and tumor recurrence ( p = 0.011) in locally advanced ESCC patients. Moreover, overexpression of Ku80 was associated with reduced OS of patients after surgery ( p = 0.001). Multivariate analysis with a Cox proportional hazards model further suggested that Ku80 expression was an independent prognostic indicator for patients' OS ( p = 0.029). Conclusions: Ku80 was a predictor of tumor's progression and prognosis of locally advanced ESCC patients. All of these results indicate that assessment of Ku80 level could improve stratification of locally advanced ESCC patients. [ABSTRACT FROM AUTHOR]

Background and Aim Common patterns of the operative failure after Ivor-Lewis esophagectomy in esophageal squamous cell carcinoma ( ESCC) patients are locoregional lymph node metastasis. It is clinically significant to investigate the biological markers to predict the subset of patients who are at higher risk of lymphatic metastatic recurrence. Our research aimed to investigate the association between the Stathmin ( STMN-1) gene expression and lymphatic metastatic recurrence in p N0 ESCC patients after surgery. Methods One hundred seventy-four patients who suffered from mid-thoracic ESCC and completely resected with Ivor- Lewis esophagectomy were enrolled in our study. The entire patients were restricted to p N0 ESCC. Tissue specimens were examined for STMN-1 expression levels by immunohistochemistry and Western blotting methods. The correlation of STMN-1 levels with clinicopathological variables, prognosis, and metastatic potential was analyzed. Results One hundred patients had STMN-1 protein overexpression (57.47%), and the patients with overexpression were accompanied by significantly higher rate of lymphatic metastatic recurrence as compared with patients who had low STMN-1 expression ( P = 0.003). Multivariable Cox regression analysis revealed that the STMN-1 protein expression and T classification were independent factors to predict the lymphatic metastatic recurrence ( P = 0.007, P = 0.000, respectively). Conclusions Even p N0 ESCC are a potential to lymphatic metastatic recurrence. Stathmin overexpression can be used as a marker to identify those patients who are at high risk for lymphatic metastatic recurrence in p N0 ESCC after an Ivor- Lewis esophagectomy. [ABSTRACT FROM AUTHOR]

Purpose: Targeted therapy has greatly improved the treatment for adenocarcinoma of the lung, but not squamous cell carcinoma (SCC) of the lung. The current paper describes the abnormalities of receptor tyrosine kinases (RTK) in lung SCC in a hope to stimulate the development of therapeutics that can have clinical impact. Methods: We reviewed both clinical and preclinical studies published in English regarding RTK abnormalities and/or RTK-targeting treatment for SCC of the lung. Results: RTK alterations have been demonstrated as biological signature for SCC of the lung. A number of clinical trials of RTK-targeting therapy have been carried out or are ongoing, with encouraging results. Conclusions: SCC of the lung should be treated as an independent disease with unique treatment options based on molecular changes, particularly RTK. [ABSTRACT FROM AUTHOR]

Aim: To investigate the correlation between vascular endothelial growth factor C (VEGF-C) expression and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Method: In all, 92 ESCC specimens were re-evaluated by reverse transcriptase-polymerase chain reaction to detect VEGF-C mRNA. Correlations between VEGF-C expression and clinicopathological factors were analyzed using χ2 test. The log-rank test was used to calculate survival rate and disease-free survival. A Cox regression multivariate analysis was performed to determine independent prognostic factors. Results: VEGF-C mRNA expression was correlated with tumor invasion ( P < 0.01), lymph node metastasis ( P = 0.025), tumor stage ( P < 0.01) and lymphatic invasion ( P < 0.001). The 5-year survival rate in patients was significantly associated with tumor invasion ( P < 0.001), lymph node metastasis ( P < 0.001), tumor stage ( P < 0.001) and VEGF-C mRNA expression ( P = 0.001). The 5-year survival rate of patients without VEGF-C mRNA expression was significantly higher than that of the patients with VEGF-C mRNA expression ( P = 0.001). Cox regression multivariate analysis confirmed that tumor invasion was the only relevant independent factor. The 5-year disease-free survival rate of patients without VEGF-C mRNA expression in esophageal cancer tissues was also significantly higher than that of the patients with VEGF-C mRNA expression ( P < 0.001). Cox regression multivariate analysis confirmed that tumor invasion and VEGF-C mRNA expression were independent factors for 5-year disease-free survival. Conclusion: VEGF-C expression correlates with poor survival in ESCC patients. However, it is not an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Purpose: To detect the expression levels of ubiquitin-specific protease 22 (USP22) in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic and prognostic data. Methods: The immunoreactivity of USP22 protein was analyzed in 157 pathologically characterized ESCC tissues by immunohistochemistry. All statistical analyses were performed with SPSS statistical software to evaluate the association of USP22 protein with clinicopathologic factors and survival. Results: High expression of USP22 protein was detected in 50.96 % of 157 ESCC tissues and significantly associated with invasion depth, lymph node metastasis, pathologic stage and tumor relapse ( P < 0.05, respectively). Univariate survival analysis showed that patients with high expression of USP22 protein had a significantly poorer 5-year disease-specific survival ( P = 0.002), and multivariate survival analysis showed that high expression of USP22 protein was an independent prognosticator for unfavorable disease-specific survival ( P = 0.039). Further survival analysis stratified by pathologic stage demonstrated that high expression of USP22 protein significantly predicted unfavorable clinical outcome ( P = 0.029) among patients with pathologic stage II-III diseases. Conclusion: USP22 protein plays an essential role in ESCC progression and has clinical potentials not only as a promising biomarker to identify the subgroup of patients with more aggressive tumors and poor prognostic potential but also as an attractively therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell cancer (ESCC) is one of the most common malignancies treated by thoracic surgeons. It is aggressive and generally associated with a poor prognosis. One of the most important prognostic factors is the presence of the lymph node metastasis (LNM). The purpose of the present study was to investigate the risk factor with lymph node metastatic recurrence in patients with N0 esophageal squamous cancer after Ivor Lewis esophagectomy based on the detection of mucin1 (MUC1) mRNA. The subjects were 82 patients with pN0 ESCC who underwent Ivor Lewis esophagectomy with two-field lymph node dissection from January 2001 to January 2005. All lymph nodes (501 stations) obtained from these patients were reevaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect MUC1mRNA. The diagnosis of lymph node micrometastasis (LNMM) was based on the detection of MUC1 mRNA. The Kaplan-Meier method was used to calculate the survival rate and lymph nodal metastatic rate. Log-rank test was performed to compare the recurrence rate, and Cox regression multivariate analysis was performed to determine independent prognostic factors. The overall 3-year survival rates of 82 patients were 78.0%, and the first recurrence exhibiting lymph nodal metastasis was recognized in 37 patients (45.1%) in the first 3 years after operation. Lymph node metastatic rate in patients in the first 3 years after operation was significantly associated with the T status ( P < 0.05). MUC1 mRNA was identified in at least one lymph node station from 23 (28.1%) patients. Also, lymph node metastatic rate of the patients with LNMM was significantly higher than that of the patients without LNMM ( P < 0.01).The results of multivariate analysis confirmed that LNMM and T status in patients with N0 ESCC were independent risk factors for 3-year lymph node metastatic recurrence after Ivor Lewis esophagectomy. Adjunctive therapy might be beneficial in controlling the locoregional recurrence and elevated healing rates for certain patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To control the postoperative local recurrence is one of the critical factors to improve prognosis of patients with esophageal carcinoma. The aim of this study is to evaluate the effectiveness of modified Ivor-Lewis esophagectomy plus adjuvant radiotherapy for local control of stage IIA squamous cell carcinoma in the mid-thoracic esophagus. Methods: One hundred and twenty-five patients with stage IIA mid-thoracic esophageal squamous cell carcinoma who underwent modified Ivor-Lewis esophagectomy between June 1999 and June 2002 were included in the retrospective analysis. All the patients were evaluated within 3 years after surgery to detect tumor recurrence. Kaplan–Meier method was used to calculate the survival rate and logistic regression analysis was performed to identify risk factors of locoregional recurrence. Results: The overall 3-year and 5-year survival rate in all patients was 58.4% and 43.2%, respectively. Tumor recurrence occurred in 61 patients (48.8%) within 3 years after operation. The median disease-free interval was 12.6 months. Thirty-three patients (26.4%) developed locoregional recurrence, 23 patients (18.4%) developed distant recurrence and 5 patients (4.0%) developed locoregional and distant recurrence simultaneously. Locoregional recurrence rate of patients with postoperative radiotherapy was significantly lower than that of those without postoperative radiotherapy (p <0.05). Logistic regression analysis showed that adjuvant radiotherapy (p =0.007) was an independent risk factor for tumor locoregional recurrence. Cox regression analysis showed that locoregional recurrence but not adjuvant radiotherapy was a relevant prognostic factor of patients with stage IIA esophageal cancer. Conclusions: Modified Ivor-Lewis esophagectomy with two-field lymph node dissection plus adjuvant radiotherapy might be an effective strategy to achieve local control of stage IIA mid-thoracic esophageal squamous cell carcinoma. [Copyright &y& Elsevier]

Despite increasingly radical surgery for esophageal carcinoma, many patients still develop tumor recurrence after operation. This study was designed to evaluate the recurrence pattern of squamous cell carcinoma in the middle thoracic esophagus after modified Ivor-Lewis esophagectomy. We retrospectively reviewed data of 196 patients who underwent modified Ivor-Lewis esophagectomy with two-field lymph node dissection from January 1997 to January 2001. Recurrence was classified as locoregional or hematogenous recurrence. Logistic regression analysis was performed to identify risk factors of postoperative recurrence. The overall 3-year and 5-year survival rates in all patients were 53% and 31%, respectively. Recurrence was recognized in 96 patients (48.9%) in the 3 years after operation. The median time to tumor recurrence was 12.2 months. The pattern of recurrence was locoregional in 52 patients (mainly mediastinal in 41, single cervical/supraclavicular in 8), hematogenous in 44 patients (simultaneous locoregional and hematogenous in 10; mainly liver, bone, or lung in 39). The locoregional recurrence rate was significantly lower in patients with postoperative radiotherapy than that in patients without postoperative radiotherapy ( p = 0.02). Logistic regression analysis showed that T3 ( p = 0.032), N1 ( p = 0.003), and postoperative radiotherapy ( p = 0.022) were independent risk factors for tumor locoregional recurrence. About one half of the patients would develop recurrent disease within 3 years after modified Ivor-Lewis esophagectomy with two-field lymph node dissection, and most of them had mediastinal lymph node, liver, bone, or lung metastasis. Postoperative radiotherapy was beneficial in the control of locoregional recurrence. [ABSTRACT FROM AUTHOR]