Overexpression of Sox3 is associated with diminished prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy lacking valid prognostic biomarkers. As a member of the High Mobility Group domain-containing DNA-binding proteins, Sox3 has been reported to induce oncogenic transformation of chicken embryo fibroblasts. However, the expression and prognostic value of Sox3 in ESCC remain unclear. METHODS: A total of 30 pairs of ESCC with a corresponding non-neoplastic esophageal epithelium (NE) specimen were investigated for Sox3 expression using RT-PCR and western blot analysis. Tissue microarrays containing 118 ESCC and 30 NE samples were detected for Sox3 expression using immunohistochemical staining. The relationship of Sox3 staining with various clinicopathological characteristics and survival of patients was statistically analyzed. RESULTS: Sox3 expression in ESCC was 3.1- and 2.7-fold higher than in NE at mRNA (P < 0.001) and protein level (P < 0.001), respectively. Positive staining of Sox3 was observed in 77.1 % of the ESCC and 16.7 % of the NE samples (P < 0.001). High expression of Sox3 was significantly correlated with the regional lymph nodes metastasis (RLNM) (P = 0.022) and advanced TNM stage (P = 0.011). Moreover, high expression of Sox3 was significantly associated with poor overall survival (P < 0.001) and recurrence-free survival (P < 0.001) in ESCC patients. Both Sox3 expression (P < 0.001) and RLNM (P = 0.002) were independent prognostic factors for patients with ESCC. CONCLUSIONS: Sox3 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for ESCC.

One surgeon's learning curve for video-assisted thoracoscopic esophagectomy for esophageal cancer with the patient in lateral position: how many cases are needed to reach competence?

BACKGROUND: Minimally invasive esophagectomy is a feasible technique shown to be safe and oncologically adequate for the treatment of esophageal cancer. This study aimed to describe one surgeon's learning curve for video-assisted thoracoscopic esophagectomy with the patient in lateral position. METHODS: From May 2010 to June 2012, 89 thoracoscopic esophagectomies for esophageal cancer were performed by one surgeon. The patients were divided into three groups. Group A included the first 30 cases. Group B comprised cases 31 to 60, and group C included the final 29 cases. The demographic characteristics and the intra- and postoperative variables were collected retrospectively and analyzed. RESULTS: One postoperative death occurred. Eight patients required conversion. No significant difference in background or clinicopathologic factors among the three groups was observed. Compared with group A, a significant decrease in intrathoracic operative time (107.7 ± 16.2 min; P = 0.0000), total operative time (326.3 ± 40.7 min; P = 0.0002), and blood loss (290.8 ± 114.3 ml; P = 0.0129) was observed in group B, whereas more retrieved nodes were harvested (20.1 ± 9.5; P = 0.0002). The last 29 patients (group C) involved significantly less intrathoracic operative time (82.8 ± 18.4 min; P = 0.0386), total operative time (294.7 ± 37.4 min; P = 0.0009), and blood loss (234.7 ± 87.8 ml; P = 0.0125) as well as a shorter postoperative hospital stay (12.4 ± 3.7 days; P = 0.0125) compared with group B. A significant decline in the overall morbidity from group A to group C (P = 0.0005) also was observed. CONCLUSIONS: The results of this study suggest that at least 30 cases were needed to reach the plateau of thoracoscopic esophagectomy. After more than 60 cases of thoracoscopic esophagectomies had been managed, lower morbidity could be obtained.

Lateral position could provide more excellent hemodynamic parameters during video-assisted thoracoscopic esophagectomy for cancer.

BACKGROUND: Thoracoscopic esophagectomy is a feasible technique that has been shown to be safe for the treatment of esophageal cancer. There continues to be controversy about the optimal position during thoracoscopic esophagectomy. In this study, we compared the intraoperative hemodynamic parameters, clinical pathological characteristics, as well as postoperative complications in patients who underwent thoracoscopic esophagectomy in the prone position (PP) or left-lateral decubitus position (LDP). METHODS: Between January 2011 and June 2011, 23 patients underwent thoracoscopic esophagectomies for cancer of the esophagus in LDP (group A). Since February 2011, we have performed thoracoscopic esophagectomies for cancer of the esophagus in PP for 21 patients (group B). The demographics and clinicopathologic factors, as well as the intraoperative hemodynamic parameters, of the two groups were analyzed. RESULTS: No postoperative death occurred in these 44 patients. Overall morbidity was similar in the two groups. No significant difference in the length of operation or number of retrieved mediastinal nodes between the two groups was observed, but the intraoperative blood loss in group A was significantly higher than in group B (P = 0.0228). There was no significant difference of the intraoperative mean arterial pressure, central venous pressure, heart rate, and stroke volume variation between the two groups and various positions. In group A, the cardiac output (CO), cardiac index (CI), as well as stroke volume index (SVI) did not exhibit significant difference after altering patients' position from LDP to SP. However, patients who underwent thorascopic esophagectomy in PP had lower CO, CI, and SVI than in LDP during the thoracoscopic stage. CONCLUSIONS: Compared with the PP, the LDP could provide more excellent hemodynamic parameters during thoracoscopic esophagectomy. However, the various hemodynamic statuses did not exert significant influence on the occurrence of postoperative complications.

The Clinical Significance and Prognostic Value of ALDH1 Expression in Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: The results of the association between aldehyde dehydrogenase 1 (ALDH1) expression and prognosis of non-small cell lung cancer (NSCLC) are contradictory. We conducted this meta-analysis to investigate the clinical significance and prognostic value of ALDH1 in NSCLC. METHODS: The databases PubMed, Web of Science, EMBASE, the Cochrane Library, Wanfang, and CNKI were systematically queried to identify eligible studies. The retrieval time was from database establishment to August 2023. We evaluated the correlation between ALDH1 expression and clinical features of NSCLC by employing odds ratios (ORs) and 95% confidence intervals (95% CIs). In addition, we used hazard ratios (HRs) and 95% CIs to evaluate the role of ALDH1 expression in the prognosis of NSCLC. RESULTS: Our study included 21 literatures involving 2721 patients. The expression of ALDH1 in NSCLC was higher than that in normal tissues (OR = 6.04, 95% CI: 1.25-29.27, P = 0.026). The expression of ALDH1 was related to TNM stage (OR = 1.81, 95% CI: 1.06-3.09, P = 0.029), tumor grade (OR = 0.29, 95% CI: 0.17-0.48, P < 0.0001), lymph node metastasis (OR = 2.60, 95% CI: 1.52-4.45, P = 0001) and histological subtype (OR = 0.67, 95% CI: 0.52-0.86, P = 0.002). In patients with NSCLC, we found that the over-expression of ALDH1 was significantly associated with poor overall survival (OS) (HR = 1.44, 95% CI: 1.15-1.81, P = 0.002) and disease-free survival (DFS) (HR = 1.74, 95% CI: 1.45-2.10, P < 0.0001). CONCLUSION: The expression of ALDH1 is closely associated with the clinicopathologic characteristics and prognosis of NSCLC. ALDH1 may serve as a valuable clinical assessment tool and prognostic predictor in NSCLC.

Zinc induces cell cycle arrest and apoptosis by upregulation of WIG-1 in esophageal squamous cancer cell line EC109.

Zinc deficiency was implicated in the etiologies of human esophageal squamous cell carcinoma (ESCC). Wild-type p53-induced gene 1 (WIG-1), a kind of zinc finger protein, was cloned from the human 3q26.3 region and encoded a putative polypeptide of 289 amino acids. Our previous studies have demonstrated that the expression of WIG-1 was downregulated in ESCC tissues. Herein, we investigated the effect of zinc on cell proliferation, apoptosis, as well as expression of WIG-1 in EC109 cells. Meanwhile, an RNAi vector of WIG-1 was transfected into EC109 cells and the effect of zinc on WIG-1 expression was investigated. We found that zinc could suppress cell proliferation and induce G0/G1 cell cycle arrest and apoptosis of EC109, and this efficacy might result from the expression altering of several apoptosis-related genes, such as Bax, p21 ( WAF ), and cyclin D1. In particular, upregulation of WIG-1 was observed after zinc supplementation, indicating that WIG-1 might be involved in the zinc-induced cell cycle arrest and apoptosis of EC109 cells by regulating the expression of Bax, p21 ( WAF ), and cyclin D1.

Effect of altered WIG-1 expression on DDP sensitivity in a DDP-resistant esophageal squamous cancer cell line.

Esophageal cancer (EC) is the most common esophageal malignancy and has a dismal prognosis. Developing novel strategies to reverse the resistance to chemotherapeutics in EC is currently of intense interest. The wide-type p53 induced gene 1 (WIG-1) is a p53-regulated transcription factor. The effect of WIG-1 on the regulation of cisplatin (DDP) sensitivity was evaluated in DDP-resistant EC cells both in vitro and in vivo. The DDP-resistant sub-line EC109/DDP was successfully selected following eight months of culture. Overexpression of WIG-1 in EC109/DDP cells significantly lowered the IC(50) of DDP to 1.11 ± 0.54 µg/ml when compared to Control cells (4.57 ± 0.98 µg/ml, P < 0.05). In addition, WIG-1 exerted a negative effect on cell proliferation and on the cloning efficiency of EC109/DDP cells. A significant increase in the apoptosis index and in TUNEL-positive nuclei was observed when the expression of WIG-1 was upregulated. Furthermore, WIG-1-overexpressing DDP-resistant EC cells exhibited suppressed xenograft tumor growth and a lower green fluorescent protein (GFP) fluorescence intensity following DDP injection. WIG-1 also reduced the expression of ERCC1 and increased the expression of Bax in DDP-resistant EC cells, while the expression of Bcl-2, P-gp and GST-π was not significantly altered after up- or down-regulation of WIG-1. In summary, these results show that WIG-1 may reverse the DDP resistance of EC cells by reducing ERCC1 expression and increasing Bax expression. This study will provide a framework for understanding the mechanism of DDP resistance by WIG-1 and will aid in the therapeutic use of DDP in ESCC.

Preparation of a novel monoclonal antibody specific for WIG-1 and detection of its expression pattern in human esophageal carcinoma.

We have efficiently generated the first monoclonal antibody (MAb) against the human WIG-1 (wild-type p53-induced gene 1) protein, an apoptosis-related protein consisting of three zinc finger domains. Protein A affinity chromatography was performed to purify MAb from mice production ascites. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA). One MAb designated GW-3E4 (IgG1), effective in detecting the nuclear protein in human esophageal squamous cell carcinoma (ESCC) tissues and EC109 cell line, was characterized by ELISA and Western immunoblotting. Thus, it binds to native WIG-1 protein and should be useful in studies of WIG-1 protein function and expression. By Western immunoblotting analysis of 20 patients with ESCC using the MAb, we found that the expression of WIG-1 protein in tumor tissue was significantly higher than in incision margin. The results showed that WIG-1 might be a novel modifier in esophageal carcinogenesis, and the WIG-1 MAb should be useful in further study of the mechanism in WIG-1-related physiological reactions.