人食管鳞癌组织中RhoC和Ki-67的表达及意义

 目的：检测人食管鳞癌组织中RhoC和Ki-67的表达,探讨它们在食管鳞癌发生发展中的作用及相关性。方法：采用免疫组织化学方法（二步法）,检测分析52例人食管鳞癌组织中RhoC和Ki-67蛋白的表达情况及其与患者临床病理特征的关系。结果：（1）食管鳞癌组织RhoC蛋白的阳性表达率为61.5%（32/52）,相应癌旁组织RhoC阳性表达率为29.7%（11/37）,差异显著（P＜0.05）。（2）RhoC表达与食管鳞癌临床TNM分期和淋巴结转移密切相关,TNM Ⅲ期食管鳞癌组织中RhoC阳性表达率为78.3%（18/23）,显著高于TNM Ⅰ～Ⅱ期的48.3%（14/29）（P＜0.05）;伴有淋巴结转移的食管鳞癌组织中RhoC阳性表达率为81.8%（18/22）,显著高于无淋巴结转移的46.7%（14/30）（P＜0.05）。（3）食管鳞癌组织中,RhoC与Ki-67的表达呈显著正相关（r=0.322,P＜0.05）,均呈升高趋势。结论：RhoC的高表达与食管鳞癌的分期、淋巴结转移及细胞增殖密切相关。RhoC可成为食管鳞癌早期诊断和判断预后的辅助指标。     

FEZ1基因在食管癌变过程中的作用

目的探讨FEZ1基因在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达及其与患者预后的关系。方法采用Western blot和免疫组化法分析FEZ1基因在ESCC中的表达情况,应用SPSS 13.0软件分析其与临床病理资料及预后的关系。结果 FEZ1蛋白阳性表达在食管癌中的表达与浸润深度、肿瘤大小相关(P<0.05);而与肿瘤组织分化程度、淋巴结转移无关(P>0.05)。正常食管组织中FEZ1的蛋白表达(4.3±0.39)明显高于食管癌组织中(1.6±0.25),且差异有显著性(P<0.05)。FEZ1的高表达提示患者的5年生存率高。结论 FEZ1基因在食管癌的发生、发展过程中起着重要的作用;FEZ1基因在食管癌中可能是候选的抑癌基因。     

Expression of RKIP,E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma and their correlations

To detect the expression of RKIP, E-cadherin and NF-kB p65 in esophageal squamous cell carcinoma (ESCC) and study their correlations. Steptavidin-peroxidase (S-P) method was employed to detect the expressions of RKIP, E-cadherin and NF-kB p65 in ESCC tissues from 77 cases and paracancerous tissues from 77 cases. The correlations between their expressions and clinicopathological indices and between the expressions of these proteins themselves were analyzed. The expressions of RKIP and E-cadherin in ESCC tissues were obviously lower than those in the paracancerous tissues (P<0.01); the expressions in ESCC tissues from cases with lymph node metastasis were lower than those from cases without lymph node metastasis (P<0.01); the expression of RKIP was positively correlated with the expression of E-cadherin in ESCC tissues (P<0.01). The expression of NF-kB p65 in ESCC tissues was correlated with clinical staging, lymph node metastasis and tumor differentiation (P<0.01); the expression of RKIP was negatively correlated with the expression of NF-kB p65 in ESCC tissues (P<0.05). Downregulation or depletion of RKIP was related to the onset and progression of ESCC, and facilitated the invasion and metastasis of ESCC by downregulating E-cadherin and upregulating NF-kB p65.     

Expression of long non-coding RNA ZEB1-AS1 in esophageal squamous cell carcinoma and its correlation with tumor progression and patient survival

Background: LncRNA ZEB1-AS1 has been identified as a tumor oncogene in hepatocellular carcinoma. However, the clinical significance in esophageal squamous cell carcinoma (ESCC) is still unknown. The aim of this study was to explore ZEB1-AS1 expression levels and evaluated its clinical significance in ESCC patients. Methods: LNCRNA ZEB1-AS1 expression was determined by quantitative real-time PCR (QRT-PCR) in 87 pairs of ESCC specimens and adjacent non-tumor tissues. Then, the association of ZEB1-AS1 expression with clinicopathological factors or survival of ESCC patients were determined. Results: LNCRNA ZEB1-AS1 was found up-regulated in ESCC tissues compared to adjacent non-tumor tissues. Increased lncRNA ZEB1-AS1 expression was significantly associated with tumor grade, depth of invasion, and lymph node metastasis. Kaplan-Meier analysis revealed that ESCC patients with high ZEB1-AS1 expression had a poorer overall survival and disease-free survival. Furthermore, multivariate analysis suggested that ZEB1-AS1 expression was identified as an independent prognostic factor in patients with ESCC. Conclusion: These results indicated that lncRNA ZEB1-AS1 was associated with tumor progression and could be an independent prognostic factor for ESCC patients.     

Squamous cell carcinoma-derived G-CSF promotes tumor growth and metastasis in mice through neutrophil recruitment and tumor cell proliferation,associated with poor prognosis of the patients

Tumor-derived G-CSF is a well-known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G-CSF in squamous cell carcinoma (SCC). High expression of G-CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR-S1M cells produce considerable amount of G-CSF, which expression is correlated with its metastatic potentials. Deletion of G-CSF in NR-S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR-S1M tumors in the mice. Mechanistically, G-CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR-S1M tumor-bearing mice, accumulation of plasma G-CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8⁺ T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G-CSF produced by NR-S1M cells facilitates tumor progression in mice through bi-functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G-CSF expression.     

The increased number of tumor-associated macrophage is associated with overexpression of VEGF-C,plays an important role in Kazakh ESCC invasion and metastasis

Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.     

Expression of Wnt11 and Rock2 protein with clinical characteristics of esophageal squamous cell carcinoma in Kazakh and Han patients

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a very poor outcome in China. Wnt11 and Rock2, new identified proteins highly associated with metastasis of many cancers, which were never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of Wnt11 and Rock2 in tissues from 265 patients with ESCC. Immunohistochemical staining was employed to detect the correlation of Wnt11 and Rock2 expression with clinicopathological features. Methods: The expression of Wnt11 and Rock2 was detected by immunohistochemistry in esophageal squamous cell carcinomas and normal esophageal tissues. A chi-square test was used to assess the statistical significance of the correlations between Wnt11, Rock2 expression and different clinicopathological parameters, respectively. Results: The high-expression of Wnt11 and Rock2 was observed in ESCCs. Seventy-five cases of ESCC (51.7%) showed a positive expression of Wnt11, which indicated a significant association with the AJCC stage (P=0.007). Ninety-eight cases of ESCC (65.5%) showed a positive expression of Rock2, which indicated a significant association with ethnic background. There were no close correlations between Rock2 expression and gender, tumor location, AJCC stage, lymph node metastasis. Specifically, the expression of Rock2 was significantly different between Hans and Kazaks ethnicities (P=0.000). In Kaplan-Meier curve analysis, no significant correlation was observed between the expression of Wnt11, Rock-2 and the poor prognosis of ESCCs. Conclusion: Our finding suggests that the over-expression of Rock2 may play an important role in the carcinogenesis and progression, and may become a new underlying molecular marker in the diagnosis and treatment in ESCC.     

Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

食管鳞状细胞癌中血管内皮生长因子C mRNA的表达及其临床意义

目的:探讨食管鳞状细胞癌中血管内皮生长因子C(VEGF-C)的表达及临床意义。方法:收集中山大学附属第一医院2009年3月~2010年2月收治的39例食管鳞状细胞癌患者,采用原位杂交法检测肿瘤组织及正常食管组织中VEGF-CmRNA的表达情况,并进行随访观察。结果:食管鳞状细胞癌组织中VEGF-CmRNA表达阳性率为71.8%(28/39),正常食管组织中表达阳性率为12.8%(5/39),两者比较差异有统计学意义(P<0.05)。VEGF-CmRNA的表达与食管鳞状细胞癌的淋巴结转移和浸润深度有关,但与性别、年龄和肿瘤组织分化程度无关。随访至死亡或2012年2月29日(以先者为准),VEGF-CmRNA阳性组生存率低于阴性组,差异有统计学意义(P<0.05)。结论:VEGF-CmRNA的表达与食管鳞状细胞癌的发展、淋巴结转移及预后有相关性。     

食管鳞癌中VEGF-C与CD44v6的表达及其与淋巴结转移的关系

目的研究食管鳞癌组织中血管内皮细胞生长因子-C(VEGF-C)与CD44v6的表达及其与淋巴结转移的关系。方法应用免疫组织化学方法对152例食管鳞癌组织进行VEGF-C与CD44v6蛋白检测结果VEGF-C与CD44v6蛋白在食管鳞癌的阳性表达为55.3%和71.7%,VEGF-C与CD44v6的表达与食管癌有无转移有显著差异(P<0.05)。结论VEGF-C与CD44v6与食管鳞癌淋巴结转移密切相关,可作为判断食管鳞癌预后的指标。     

Overexpression of UQCRC2 is correlated with tumor progression and poor prognosis in colorectal cancer

Ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) is an important subunit of mitochondrial respiratory complex III. However, its role in tumorigenesis and tumor progression remains unknown, especially with regards to colorectal cancer (CRC). In this research, we measured the expression of UQCRC2 protein by immunohistochemistry assay in 89 paired paraffin-embedded tumor tissues and corresponding adjacent normal tissues from patients with colorectal adenocarcinoma and investigated possible correlations of UQCRC2 expression with clinicopathological parameters and prognosis. We found that UQCRC2 was significantly upregulated in CRC tissues compared with adjacent normal tissues, and immunohistochemical UQCRC2 status was correlated to the depth of invasion (T), lymph node metastasis (N), advanced TNM stage. Multivariate analysis indicated that UQCRC2 remained an independent prognostic factor for poorer overall survival. Furthermore, we determined the role of UQCRC2-knockdown in CRC cells (RKO and HCT116) using lentivirus-mediated small hairpin RNAs (shRNAs). The effects of UQCRC2 knockdown on CRC cells (RKO and HCT116) proliferation were analyzed by cell proliferation and colony formation assay, and cell cycle and apoptosis were assessed by flow cytometry. We found that silencing UQCRC2 suppressed cell proliferation and colony formation in RKO and HCT116 cells, led to a cell cycle arrest and induced cell apoptosis in vitro. These results provided novel insights into the potential role of UQCRC2 in the tumorigenesis and progression of CRC, and revealed that UQCRC2 may serve as a new prognostic and therapeutic target in CRC.     

miR-4746促进PRKACB表达上调并促进食管鳞癌细胞增殖

目的研究miR-4746在食管鳞癌中的表达及其对食管鳞癌细胞的增殖的影响。方法收集食管鳞癌患者的癌组织和癌旁组织标本,RT-PCR和Western blot检测miR-4746和PRKACB的表达,并分析二者mRNA水平的相关性。培养EC9706、HET-1A、TE-1细胞,并转染miR-control、miR-4746 mimic或inhibitor,RT-PCR检测PRKACB的表达水平,MTT法检测细胞的增殖水平。结果在食管鳞癌患者的标本中,癌组织中miR-4746和PRKACB的表达显著低于癌旁组织,miR-4746和PRKACB的表达水平呈正相关。在转染miR-4746 mimic后,PRKACB的表达上调,EC9706、HET-1A、TE-1细胞的增殖受到促进;在转染miR-4746 inhibitor后,PRKACB的表达下调,EC9706、HET-1A、TE-1细胞的增殖受到抑制。结论miR-4746促进PRKACB表达上调,并促进食管鳞癌细胞的增殖。     

ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma

Background

A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker.

新疆哈族和汉族食管癌中Toll样受体的表达及其与肿瘤细胞浸润和转移的关系

目的探讨Toll样受体TLR 4、7、9 mRNA和蛋白在新疆不同民族食管癌组织中的表达及其与肿瘤浸润和转移之间的关系。方法应用实时荧光定量PCR(qRT-PCR)法检测40例食管癌及相应癌旁组织中TLR4、7、9 mRNA的表达。采用免疫组化SP法检测90例食管癌及相应癌旁组织中TLR4、7、9蛋白的表达。结果 TLR7、9 mRNA在食管癌中的表达量明显高于癌旁组织(P<0.05);TLR4 mRNA在食管癌中的表达量与癌旁组织中的表达,差异无统计学意义(P>0.05)。TLR4、7、9 mRNA在汉族食管癌患者组织中的表达均高于新疆哈萨克族(哈族)(P<0.05)。TLR4、7、9蛋白在食管癌组织中的表达明显高于癌旁组织(P<0.05)。TLR4表达与肿瘤淋巴结转移密切相关(P<0.05);TLR7表达与肿瘤浸润深度相关(P<0.05);TLR4、7、9蛋白表达与肿瘤的分化程度密切相关(P<0.05)。TLR4蛋白在食管癌组织间质炎细胞中高表达与肿瘤的浸润和转移有关,而TLR9蛋白在食管癌组织间质成纤维样细胞中高表达与肿瘤的低浸润和低转移密切相关(P<0.005)。结论TLR4、7、9在食管癌中的高表达与食管癌生物学行为密切相关,提示该基因在食管癌的发生、发展、浸润及转移中起一定作用,其族群差异可能反应不同族群的遗传背景及肿瘤的发病机制。     

P53和1d2蛋白在食管鳞状细胞癌的表达及其意义

目的研究P53、Id2蛋白在食管鳞状细胞癌组织的表达及其意义。方法采用免疫组织化学SP法和图像分析技术检测122例食管鳞状细胞癌及90例癌旁正常组织中P53、Id2的表达情况。结果122例食管鳞状细胞癌中P53、Id2表达水平均高于癌旁正常组织（P〈0．01）。P53表达强度与患者的性别、年龄及肿瘤的分化程度未见明显相关性（P〉0．05）,但与肿瘤的浸润深度及淋巴结转移情况相关（P〈0．05）;Id2的表达与患者的性别、年龄及淋巴结转移情况未见明显相关性（P〉0．05）,但与肿瘤的分化程度成负相关（P〈0．05）,且与肿瘤浸润深度正相关（P〈0．05）。结论P53、Id2在食管鳞状细胞癌的高表达可能作为判断食管鳞状细胞癌生物学行为的潜在指标。     

CD51 is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma

Background

Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and some other parts of the world with a dismal prognosis. CD51 (integrin αv),a transmembrane glycoprotein responsible for cell-to-matrix binding has been found to enhance tumor progression. However, its expression and clinicopathological significance in ESCC tumors are not fully understood. The purpose of this study was to investigate the expression level of CD51 and to explore its clinicopathological significance in ESCC.

人食管癌细胞株KYSE-150、TE-1中肿瘤干细胞的培养分化及增殖侵袭能力分析

BACKGROUND: There is a certain cell subset in esophageal cancer tissues, with certain invasive and metastatic properties, which is closely related to the clinical therapeutic effect on tumors. OBJECTIVE: To isolate tumor stem cell spheres in human esophageal carcinoma cell lines KYSE-150 and TE-1 and to analyze their proliferation and invasion ability. METHODS: KYSE-150 and TE-1 cells were cultured in serum-free medium to observe the formation of cell spheres. Cell proliferation and invasion were detected using MTT and Transwell chamber culture. Surface markers of cells were detected using flow cytometry. RESULTS AND CONCLUSION: Cell spheres that were stably subcultured were obtained from KYSE-150 and TE-1 cells cultured in serum-free medium. The proliferation and invasion abilities of cell spheres were significantly stronger than those of parent cells (P < 0.05). The number of CD44+, CD271+ and CD44+CD271+ cells in TE-1 and KYSE-150 cell spheres was significantly higher than that in the TE-1 and KYSE-150 parent cells (P < 0.05). These experimental results show that cell spheres isolated from human esophageal carcinoma cell lines TE-1 and KYSE-150 have tumor stem cell properties as well as strong proliferation and invasion abilities. And moreover, CD44 and CD271 can be used as important surface markers of esophageal carcinoma stem cells.      

受体相互作用蛋白1RIP1在食管鳞癌的表达及意义

目的明确受体相互作用蛋白1 RIP1在人食管鳞癌组织中的表达及与临床病理因素、病人预后的关系。方法使用免疫组化SP法检测76例人食管鳞癌组织和相对应的癌旁正常食管黏膜中RIP1的表达状况,并分析与临床病理因素如病人的性别、年龄、肿瘤大小、浸润深度、临床分期、分级、有无淋巴结转移的关系,并进行了随访。结果76例食管鳞癌中RIP1阳性的病例有53例,占69.7%,癌旁组织RIP1阳性的只有19例,占25%,差异有统计学意义,RIP1的阳性表达与病人的性别、年龄、肿瘤大小无关,与浸润深度、临床分期、分级、有无淋巴结转移成正相关,随访结果表明:食管鳞癌中RIP1阳性率越高,病人生存期越短,预后越差,RIP1蛋白的表达是个预后不良的独立因素。结论 RIP1在食管鳞癌中表达增高,可能参与食管鳞癌的发生。