[show abstract][hide abstract] ABSTRACT: In our previous study, Human Signal Transduction in Cancer Gene Array was used in 12 fresh tumor samples to detect the gene expression profiles in the esophageal squamous cell carcinoma (ESCC) tissues matched adjacent non-cancerous samples. Among genes up-regulated at least twofold, β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 were found. So subsequently, the aim of this study was to investigate the prognosis and clinicopathologic roles of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC tissue. The mRNA and protein expression levels of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 genes in 70 ESCC and adjacent non-cancerous paraffin-embedded samples were determined by Real-Time Quantitative PCR (RT-PCR) and immunohistochemical staining. The mRNA expression level of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC was significantly higher than that in the adjacent non-cancerous tissues (0.0821 ± 0.0416 vs. 0.0185 ± 0.0201, P = 0.0000; 1.9934 ± 1.9888 vs. 0.8863 ± 0.665, P = 0.0184; 0.0298 ± 0.0215 vs. 0.0189 ± 0.0187, P = 0.0017; 2.098 ± 0.091 vs. 1.016 ± 0.078, P = 0.0000; 2.181 ± 2.158 vs. 0.931 ± 0.894, P = 0.0152; respectively), and the protein expression level of determined genes was also significantly higher than that in the adjacent non-cancerous tissues (0.2835 ± 0.0844 vs. 0.2352 ± 0.0670, P = 0.0003; 0.3830 ± 0.0947 vs. 0.2721 ± 0.1474, P = 0.0000; 0.2637 ± 0.0348 vs. 0.2042 ± 0.0180, P = 0.0000; 0.2058 ± 0.0316 vs. 0.1218 ± 0.0518, P = 0.0000; 0.2736 ± 0.0834 vs. 0.2251 ± 0.0571, P = 0.0001; respectively). Then, the overexpression of mRNA and protein levels of β-catenin, Wnt1 and Bmi-1 was aggressively associated with lymph node metastasis, advanced pathological stage, and prognosis of the patients with ESCC (P < 0.05). The up-expression of Hoxa9 mRNA and protein was also aggressively associated with lymph node metastasis and advanced pathological stage (P < 0.05); however, the overexpression of Hoxa9 protein was not associated with the prognosis (P > 0.05). Meanwhile, the hypo-expression of Smad4 mRNA was aggressively associated with advanced pathological stage and prognosis of the patients with ESCC (P < 0.05); however, the hypo-expression of Smad4 protein was neutral to the prognosis and lymph node metastasis (P > 0.05). β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 protein expression analysis showed that the positive outcomes of the combined detection of Wnt1 and β-catenin expression or Wnt1, β-catenin and Bmi-1 expression were significantly worse than those of a single target protein expression (P < 0.05). Meantime, the prognosis of the combined positive expression of Wnt1, β-catenin, and Bmi-1 was poorer than that in the combined positive expression of Wnt1 and β-catenin (P < 0.05). The prognosis of ESCC patients with the overexpression of Wnt1/β-catenin and Bmi-1 was relatively poor, and the level of Wnt1/β-catenin and Bmi-1 was conversely correlated with advanced pathological stage and lymph node metastasis. The expression level of Smad4 and Hoxa9 mRNA was also associated with the prognosis of the patients with ESCC, pathological stage, and lymph node metastasis; however, they might not be the independent prognostic factor.
Medical Oncology 01/2011; 29(1):151-60. · 2.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the role of postoperative chemoradiotherapy (CRT) as a multimodality treatment option for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by a prospective comparison between surgery alone and postoperative CRT.
Using preoperative computed tomography (CT)-based staging criteria, 158 patients with ESCC (stage II-III) were enrolled in this prospective study. With informed consent, the patients were randomized into two groups: postoperative CRT (78 cases) and surgery alone (S, 80 cases). After a few minor adjustments to the enrolled patients, the actual patients of postoperative CRT group and S group were 74 cases and 77 cases, respectively. Comparison of the complications, local recurrence rate, distant metastasis rate, survival rate and progression-free survival in the two groups was carried out.
With a median follow-up of 37.5 months, the 1-, 3-, 5-, 10-year overall survival (OS) rates were 91.0%, 62.8%, 42.3%, 24.4% and 87.5%, 51.3%, 33.8%, 12.5% for the postoperative CRT and S arm, respectively. A significant difference in OS was detected between the two arms (P = 0.0276). There was a significant difference of progression-free survival (PFS) between the two arms (P = 0.0136). The local recurrence rates in the postoperative CRT group and S group were 14.9% and 36.4%, respectively (P < 0.05). No significant difference was detected between the complications of the two groups (P > 0.05). Toxicities of chemoradiotherapy in the postoperative CRT arm were moderate, which can be relieved rapidly by adequate therapy.
Rational application of postoperative chemoradiotherapy can provide a benefit in progression-free survival and overall survival in patients with locally advanced esophageal squamous cell carcinoma.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2010; 32(6):452-5.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the correlation between Wnt1/beta-catenin expression and the clinicopathologic features and prognosis of patients with esophageal squamous cell carcinoma (ESCC). The mRNA and protein expression levels of Wnt1/beta-catenin genes in 70 ESCC and 15 adjacent noncancerous paraffin-embedded samples were determined by real-time quantitative polymerase chain reaction and immunohistochemical staining. The mRNA expression level of Wnt1/beta-catenin in ESCC was significantly higher than that in the adjacent noncancerous tissues (1.9934 +/- 1.9888 vs. 0.8863 +/- 0.665, p = 0.0184; 0.2854 +/- 0.1298 vs. 0.0128 +/- 0.0158, p = 0.0000, respectively), and the overexpression of Wnt1/beta-catenin mRNA was aggressively associated with lymph node metastasis and advanced pathological stage (p < 0.0001). The protein expression level of Wnt1/beta-catenin was also significantly higher than that in the adjacent noncancerous tissues (0.3830 +/- 0.0947 vs. 0.2721 +/- 0.1474, p = 0.0002; 0.2835 +/- 0.0844 vs. 0.2352 +/- 0.0670, p = 0.0210, respectively); however, the overexpression was not associated with clinicopathologic characteristics. Meanwhile, the protein expression level of Wnt1 had no relevance with that of beta-catenin. The overexpression of Wnt1/beta-catenin might be an important molecular marker to predict the clinicopathologic stage and prognosis of ESCC, and the level of Wnt1/beta-catenin mRNA was conversely correlated with lymph node metastasis and advanced pathological stage. The overexpression of Wnt1/beta-catenin mRNA should also predict poor prognosis of ESCC; however, it might not be an independent prognostic factor.
[show abstract][hide abstract] ABSTRACT: To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis.
PubMed and manual searches were done to identify all published randomized controlled trials (RCTs) that compared neoadjuvant chemoradiotherapy plus surgery (CRTS) with surgery alone (S) for esophageal cancer. According to the test of heterogeneity, a fixed-effect model or a random effect model was used and the odds ratio (OR) was the principal measure of effects.
Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C (Cochrane Reviewers' Handbook 4.2.2). OR (95% CI, P value), expressed as CRTS vs S (values > 1 favor CRTS arm), was 1.19 (0.94-1.48, P = 0.28) for 1-year survival, 1.33 (1.07-1.65, P = 0.69) for 2-year survival, 1.76 (1.42-2.19, P = 0.11) for 3-year survival, 1.41 (1.06-1.87, P = 0.11) for 4-year survival, 1.64 (1.28-2.12, P = 0.40) for 5-year survival, 0.82 (0.39-1.73, P < 0.0001) for rate of resection, 1.53 (1.33-2.84, P = 0.007) for rate of complete resection, 1.78 (1.14-2.78, P = 0.79) for operative mortality, 1.12 (0.89-2.48, P = 0.503) for all treatment mortality, 1.33 (0.94-1.88, P = 0.04) for the rate of adverse treatment, 1.38 (1.23-1.63, P = 0.0002) for local-regional cancer recurrence, 1.28 (0.85-1.58, P = 0.60) for distant cancer recurrence, and 1.27 (0.86-1.65, P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients. The 5-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR: 1.45, 95% CI: 1.26-1.79, P = 0.015) instead of sequentially (OR: 0.85, 95% CI: 0.64-1.35, P = 0.26).
Compared with surgery alone, neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence. Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.
World Journal of Gastroenterology 10/2009; 15(39):4962-8. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the clinicopathological roles of Bmi1 in esophageal squamous cell carcinoma (ESCC).
Quantitative real-time polymerase chain reaction and immunohistochemical staining for Bmi1 were performed in cancerous and adjacent non-cancerous paraffin-embedded esophageal specimens.
The Bmi1 expression level was unaffected by gender and age. The level of Bmi1 mRNA in ESCC was significantly higher than that in the adjacent non-cancerous tissues (2.181 +/- 2.158 vs 0.931 +/- 0.894, P = 0.0152), and its over-expression was aggressively associated with lymph node metastasis (3.580 +/- 2.487 vs 1.703 +/- 0.758, P = 0.0003), poorer cell differentiation (P = 0.0000) and advanced pathological stage (3.827 +/- 2.673 vs 1.590 +/- 0.735, P = 0.0001). The patients were divided into high-expression and low-expression groups based on the median expression level of Bmi1 mRNA, and a shorter overall survival time in the former group was observed. Immunohistochemistry for Bmi1 oncoprotein showed diffusely positive, focally positive and negative expression in 44, 16 and 10 of 70 ESCC cases, respectively, compared with three, two and five of 10 adjacent non-cancerous cases (P = 0.027). The positive rate of the oncoprotein in samples of histological grade III was higher than that of grade II (P = 0.031), but its expression had no relation to the lymph node metastasis and pathological staging. In 70 ESCC samples, Bmi1 showed high intense expression in the cytoplasm and less or even no expression in the nucleus.
Bmi1 was over-expressed in ESCC. Increased Bmi1 mRNA expression was significantly associated with ESCC progression, and the oncoprotein was largely distributed in the cytoplasm of tumor cells.
World Journal of Gastroenterology 06/2009; 15(19):2389-94. · 2.55 Impact Factor