Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is widely known as a highly fatal cancer, and thus it is important to identify tumor-specific and radiosensitivity-specific markers in ESCC. B cell translocation gene 2 (BTG2) has been considered a novel tumor suppressor gene or radiotherapy sensitivity-associated gene. However, the relationship between BTG2 and ESCC development and radiotherapy sensitivity is uncertain. The present study aims to explore the expression and clinical significance of B cell translocation gene 2 (BTG2) in ESCC by analyzing the RNAseq data from the TCGA and immunohistochemical staining of ESCC samples. We found that the level of BTG2 mRNA was significantly decreased in ESCC patients, and further decreased significantly in radiotherapy resistant patients compared to sensitive patients. The positive expression rate of BTG2 protein was 56.0% (103/184) in 184 ESCC tissue samples and 84.0% (42/50) in normal esophageal mucosal samples, respectively. The positive ratios of BTG2 expression in radiotherapy-sensitive group and radiotherapy resistant group were 57.9% (22/38) and 23.5% (4/17), respectively. Furthermore, the analysis indicates that the expression level of BTG2 significantly correlated with lymph node metastasis and clinical staging in ESCC patients. A multivariate analysis with Cox regression model showed that BTG2 level was an independent risk factor affecting the prognosis of ESCC patients. Above all, the downregulation of BTG2 may be used as a molecular marker to identify and predict ESCC progression and radiosensitivity.     

Absence of human papillomavirus DNA detected by polymerase chain reaction in French patients with esophageal carcinoma

Recent studies have suggested that esophageal human papillomavirus infection could be a risk factor for esophageal squamous cell carcinoma. The aim of this study was to evaluate the prevalence of human papillomavirus DNA sequences in the esophagus of French patients with esophageal squamous cell carcinoma. Multiplex polymerase chain reactions with consensus primers directed to the L1 gene or specific primers for human papillomavirus types 6, 11, 16, 18, 31, and 33 directed to E6 gene (40 cycles followed by restriction mapping of the amplified products) were used to determine the presence of human papillomavirus DNA sequences in esophageal squamous cell carcinoma (n = 75), normal adjacent mucosa (n = 49), and metastatic lymphadenopathies (n = 5). As an internal control, a target located in the embryonic myosin heavy-chain gene was used in each reaction. Human papillomavirus DNA sequences could not be detected in any of the tumoral samples, the normal adjacent mucosa, or the metastatic lymphadenopathies. Human papillomavirus seems not to be implicated in esophageal carcinogenesis, at least in French patients, because the viral genomes are not associated with esophageal squamous cell carcinomas.     

Slug和SRF在食管癌中的表达及临床意义

目的研究锌指转录因子Slug和血清反应因子(SRF)在食管鳞癌中的表达及其临床意义。方法收集2010年9月至2013年9月食管鳞癌手术根治标本120例,术前均未行放疗、化疗,术后常规取食管鳞癌组织包埋制备蜡块;另取距离肿瘤5 cm的食管组织60例做正常对照。按食管鳞癌诊治规范分析相关资料。所有组织蜡块常规切片三张,一份行常规HE染色,常规病理观察;另两份采用免疫组化法(SABC)检测Slug和SRF蛋白的表达水平,分析其与肿瘤大小、分化程度、浸润深度、淋巴结转移等临床生物学行为的关系。结果 Slug蛋白在食管鳞癌组中的阳性表达率显著高于正常食管黏膜组,差异有统计学意义(P>0.05);SRF蛋白在食管鳞癌组中的阳性表达率显著高于正常食管黏膜组,差异有统计学意义(P<0.05);Slug在食管鳞癌组织中的蛋白表达与肿瘤大小、分化程度、浸润深度以及淋巴结转移差异无统计学意义(P>0.05);SRF在食管鳞癌中的蛋白表达与肿瘤大小、分化程度和是否淋巴结转移无关,差异无统计学意义(P>0.05)。浸润深度中,浆膜+浆膜外组表达阳性率显著高于黏膜+肌层组(P<0.05)。结论 Slug、SRF在食管鳞癌中高表达,并与浸润深度相关,可能参与了食管鳞癌的发生、发展,并在食管鳞癌的侵袭中起到重要的调节作用。     

肌动蛋白凝胶蛋白在食管鳞癌中的表达及其与临床病理因素的关系

目的探讨肌动蛋白凝胶蛋白(Transgelin)在食管鳞癌组织中的表达及其与临床病理因素间的关系。方法采用免疫组化法检测Transgelin在食管鳞癌组织、癌旁不典型增生组织及正常食管黏膜组织中的表达,并分析Transgelin的表达与患者临床病理因素特征的关系及其对预后的影响。结果Transgelin在食管鳞癌中的阳性率明显高于癌旁不典型增生组和正常食管黏膜组织,其差异有统计学意义(P<0.05)。Transgelin在食管癌中的表达与患者的的TNM分期(P<0.05)、淋巴结转移(P<0.05)、远处转移(P<0.05)有关;与患者的性别、年龄、肿瘤直径无关(P>0.05)。在随访的210例患者中,Transgelin的生存曲线显示,高表达组Transgelin的5年生存率明显低于低表达组(P<0.05)。单因素生存分析显示,Transgelin的表达水平、TNM分期、淋巴结转移、远处转移与食管鳞癌患者术后生存时间相关。同时,多因素Cox比例风险回归模型分析显示,Transgelin的表达水平、TNM分期、淋巴结转移和远处转移为食管鳞癌患者预后的独立危险因素。结论Transgelin在食管鳞癌组织中呈高表达,其表达与食管鳞癌的发生发展和侵袭转移相关,Transgelin对于术后食管鳞癌患者的预后评估具有参考价值。     

Expression and association of CD44v6 with prognosis in T2-3N0M0 esophageal squamous cell carcinoma

Aim

To investigate the expression of CD44v6 in stage T2-3N0M0 esophageal squamous cell carcinoma (ESCC) and its prognostic significance.

Methods

The expression of CD44v6 in a series of 227 ESCC specimens was evaluated by immunohistochemistry (IHC). A reproducible semiquantitative method which took both staining percentage and intensity into account was applied for IHC scoring, and receiver operating characteristic (ROC) curve analysis was utilized to select the cut-off score for high or low IHC reactivity. Then, the correlations of CD44v6 expression with clinicopathological features of patients and its prognostic relevance were determined.

Results

In the present study, the proportion of low CD44v6 expression was found significantly lower in Grade 3 of ESCC, than that of Grade 1 and Grade 2 of ESCC. There are no significant correlations between CD44v6 expression and other clinicopathological parameters including gender, age, tumor size, tumor location, depth of invasion and pathological stage. The Kaplan-Meier survival curves showed that up-regulated expression of CD44v6 indicated a poorer post-operative survival for ESCC patients of stage T2-3N0M0 (P=0.009), especially for those with T2 lesions (P=0.044) or with stage IIB diseases (P=0.005). Multivariate analysis also confirmed that CD44v6 expression [relative risk, 1.639; 95% confidence interval (CI): 1.142-2.354, P=0.007] and depth of invasion (relative risk, 1.487; 95% CI: 1.063-2.080, P=0.020) were independent prognostic factors.

Conclusions

Elevated CD44v6 expression may be an adverse prognostic indicator for patients with stage T2-3N0M0 ESCC, especially for those with T2 lesions or stage IIB diseases.     

High expression of biglycan is associated with poor prognosis in patients with esophageal squamous cell carcinoma

Biglycan (BGN), an extracellular matrix component, has been reported to play a crucial role in the tumor progression of various cancers. However, the relation between the expression of BGN and clinical prognosis has not been studied yet. We therefore carry out the present study to elucidate the role of BGN in predicting outcomes of patients with esophageal squamous cell carcinoma (ESCC). In this study, the expression of BGN in 170 cases of ESCC tissues and matched 46 adjacent non-tumorous tissues was measured by quantitative real-time PCR and immunohistochemistry. Upregulation of BGN occurred in approximately 60% of primary ESCCs compared with their non-tumor counterparts. In addition, high expression of BGN was significantly associated with clinical stage (P = 0.009), tumor invasion (P = 0.006) and lymph node metastasis (P = 0.046). The 5-year disease-specific survival (DSS) in high expression of BGN group is poorer than that in low level expression group (36.8% VS 57.4%, P = 0.006). Stratified analysis according to the pathological stage revealed its discernibility on DSS was only pronounced in patients with advanced clinical stage (P = 0.010). Cox multivariate analysis revealed that pathologic N category (P < 0.001; hazard ratio, 2.482, 95% CI, 1.576-3.909) and BGN expression (P = 0.019; hazard ratio, 1.713, 95% CI, 1.092-2.688) were two independent prognostic factors. The findings of the present study provide evidence that BGN represents a potential novel prognostic biomarker for resected ESCC patients in advanced clinical stage.     

microRNA-155 acts as an oncogene by targeting the tumor protein 53-induced nuclear protein 1 in esophageal squamous cell carcinoma

MicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the function of miR-155 is largely unknown in esophageal squamous cell carcinoma (ESCC). In the present study, we found that miR-155 is dramatically increased in ESCC tissues compared with the paired adjacent normal tissues, which suggested that miR-155 acts as an oncogene in ESCC. We predicted that tumor protein p53-induced nuclear protein 1 (TP53INP1) is a candidate target gene of miR-155 given that miR-155 expression decreased mRNA and protein levels of TP53INP1 as determined by RT-PCR and Western blot analysis. In addition, miR-155 and TP53INP1 showed a negative relation in ESCC tissues. Dual luciferase-based reporter assay indicated direct regulation of TP53INP1 by miR-155. Furthermore, we demonstrated that RNA interference of TP53INP1 increased the proliferation and colonies formation of EC-1 cells. Up-regulation of TP53INP1 abrogated miR-155 induced growth in EC-1 cells and mutation of TP53INP1 in 3’-UTR restored the effects when co-transfected with miR-155. We also indicated that overexpression of miR-155 significantly promoted the proliferation of EC-1 cells in vitro and the development of tumors in nude mice. Taken together, our study reveals that miR-155 acts as an oncogene by targeting TP53INP1 in ESCC.