High expression of FOXC1 is associated with poor clinical outcome in non-small cell lung cancer patients

The aim of this study was to detect FOXC1 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Expressional levels of FOXC1 mRNA and protein in 30 cases of NSCLC and corresponding non-tumor tissue samples were examined by quantitative real-time PCR and Western blotting. Immunohistochemistry was performed to detect the expression of FOXC1 in 125 NSCLC tissues. We found that the expression levels of FOXC1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level FOXC1 expression was correlated with poor tumor differentiation, tumor–node–metastasis stage, and lymph node metastasis. Patients with high expression levels of FOXC1 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high FOXC1 protein expression was an independent prognostic factor for NSCLC patients. Our study suggests that over-expression of FOXC1 may play an important role in the progression of NSCLC, and FOXC1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.     

Expression of Coxsackievirus and Adenovirus Receptor in Human Lung Cancer: Possible Clinical Significance

OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy.METHODS CAR expression was assessed immunohisto-chemically in tumoral, paraneoplastic and normal samples from 112 lung cancer patients. At the same time, the mRNA and protein expression of CAR in 32 cases were determined by RT-PCR and Western blot. The relationship between CAR expression and clinicopathologic parameters was statistically analyzed.RESULTS There was no expression of CAR in normal lung tissue but a little in paraneoplastic tissue. The positive rate was 43% in squamous cell carcinoma, and 70% in adenocarcinoma.Both were much significantly higher than that in paraneoplastic tissue. The CAR expression level in adenocarcinoma was higher than that in squamous cell cancer, mRNA expression by RT-PCR and protein expression by Western blot were consistent with immunohistochemistry results.CONCLUSION CAR is overexpressed in human lung cancer,especially in adenocarcinoma. This data offer the reliable basis for adenovirus-mediated gene therapy of lung cancer; more important, CAR may take part in the formation or development of lung cancer; this may be exploitable for the development of antibody-directed therapy in human lung cancer.     

Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior

This is the first report about human tenascin-W, the fourth and final member of the extracellular matrix protein family of tenascins. Sixty-three human breast tumor extracts were analyzed by Western blotting for the presence of tenascin-W and compared with tenascin-C, an established marker of tumor stroma. Interestingly, we found tenascin-W expression in the majority of the tumor tissues, but no detectable expression in the normal mammary parenchyma. Eighty-one percent of the breast tumor samples were tenascin-W positive and 86% showed expression of tenascin-C. However, tenascin-W and tenascin-C amounts varied greatly between tumors and some contained either tenascin-W or tenascin-C exclusively, indicating independent mechanisms regulating their expression. Although there was no difference between high- or low-grade tumors with respect to the presence of tenascin-C, tenascin-W was more prominent in low-grade tumors. For 42 of the breast cancer tissues, a frozen tumor microarray was available to confirm the Western blot data by immunohistochemistry. Similar to tenascin-C, tenascin-W was detected in the tumor stroma. Fibroblasts adhered to tenascin-W in a beta(1) integrin-dependent manner and spread with a distinctive morphology under conditions where they remained round on tenascin-C. CHOB2 cells expressing alpha(v)beta(1) or alpha4beta(1) integrins were able to spread on tenascin-W. Furthermore, addition of tenascin-W to the culture medium increased migration of breast cancer cells toward a fibronectin substratum in vitro. These data imply that tenascin-W expression in the activated tumor stroma facilitates tumorigenesis by supporting the migratory behavior of breast cancer cells.     

Up-regulation of focal adhesion kinase in non-small cell lung cancer

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase linked to the integrin and growth factor receptor-signalling pathways that regulates a number of the biological processes involved in neoplastic transformation, invasion and metastases, such as cell adhesion, migration and apoptosis. Its up-regulation might play a role in the tumourigenesis of invasive tumours, but its involvement in human lung cancer tissues has not yet been determined. We immunohistochemically compared FAK expression and localisation in 60 formalin-fixed and paraffin-embedded non-small cell lung cancer (NSCLC) tissues with that in the surrounding non-neoplastic tissue and in a further five microscopically normal lungs. FAK mRNA levels were quantitatively determined by real-time RT-PCR in frozen tissue specimens of all of the tumours and 21 matched non-neoplastic lung parenchymas, and protein expression in 16 homogenates of the matched neoplastic/non-neoplastic specimens was evaluated by Western blotting. The three different techniques showed that FAK is weakly expressed in non-neoplastic lung parenchyma and up-regulated in NSCLCs. Moreover, Western blotting and real-time RT-PCR indicated a statistically significant correlation between FAK up-regulation and higher disease stages (I+II versus III+IV, p=0.019 and 0.028, respectively). Our results provide evidence that FAK is up-regulated in NSCLCs, and suggest its potential involvement in lung cancer progression.     

酪氨酸激酶受体KIT在肺癌中的表达及其意义

目的探讨KIT在肺癌中的表达及其意义.方法用RT-PCR和免疫组化方法检测了49例手术肺癌标本及9例正常肺组织中KIT在mRNA和蛋白水平上的表达.结果RT-PCR和免疫组化结果相一致,KIT受体蛋白在30%(3/10)的肺腺癌,14.4%(2/14)的鳞癌,40%(4/10)的未分化癌以及46.7%(7/15)的小细胞肺癌表达,而在正常的支气管上皮细胞中不表达.结论KIT受体在肺癌细胞中异常表达,可作为肺癌的标志,有助于肿瘤的诊断并为肿瘤的治疗提供新的潜在靶点.     

Overexpression of the eukaryotic translation initiation factor 4G (eIF4G-1) in squamous cell lung carcinoma

eIF4G-1 belongs to the family of translational initiation factors and is recognized as the central organizing protein in recruitment of mRNA during translational initiation. Previously published studies have provided some evidence that overexpression of translational factors is a general event in the process of carcinogenesis. We have characterized the expression of the eIF4G-1 protein in 33 squamous cell carcinoma (SCC) of the lung by Western blotting. Overexpression of the eIF4G-1 protein was detected in 61% of the tumors compared to the respective normal lung tissue. In addition, we analyzed the expression of this protein by immunohistochemistry in 138 SCC of the lung using a newly generated antibody that is specific for eIF4G-1 as determined by Western blotting. This anti-eIF4G-1 antibody was suitable for the immunohistochemistry of paraffin-embedded tissues. There is a strong cytoplasmic staining detected in the tumor areas that is consistent with the cytoplasmic localization of the translation factor eIF4G-1. In 72% of the examined tissue sections of SCCs of the lung, we detected an overexpression of the eIF4G-1 protein compared to the surrounding connective tissue. Two tumors that were analyzed by both methods showed an overexpression of eIF4G-1 both with Western blot analysis and immunohistochemical staining. Overexpression of eIF4G-1 may result in an increased amount of the translation initiation complex eIF4F, which in turn may activate the translation of the same target mRNAs as eIF4E.     

肺癌中SPARC和TGFβ1的表达及意义

目的 探讨肺癌组织中SPARC和TGFβ1的表达及相互关系。方法 采用原位杂交法检测SPARC mRNA和TGFβ1 mRNA在71例肺癌和30例癌旁正常组织中的表达。结果 （1）SPARC mRNA在肺癌中的阳性表达高于癌旁正常肺组织（P<0.05）,在癌组织中主要表达于间质纤维细胞中,其在肺癌组织中的表达与肺癌的临床分期及淋巴结转移有关（P均<0.05）。（2）TGFβ1 mRNA在肺癌中的阳性表达高于癌旁正常肺组织（P<0.05）,其在肺癌组织中的表达与肿瘤大小、临床分期及淋巴结转移有关（P均<0.05）。（3）SPARC mRNA和TGFβ1 mRNA在肺癌中的表达呈负相关性（r=-0.356,P=0.002）。结论 肺癌组织中SPARC的高表达可以抑制肺癌的进展,而TGFβ1的高表达可促进肺癌的进展,并参与肺癌的转移过程。此二者在肺癌的发生、发展中可能起着重要的作用。     

Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance

BACKGROUND: To investigate the relationship between the expression of glucose-regulated protein94 (GRP94) and GRP78 at the level of mRNA and protein in vivo and in human lung cancer. METHODS: RT-PCR, real-time PCR, immunohistochemistry and/or Western blot were used in 54 cases of lung cancer and corresponding normal lung tissue. RESULTS: The expression pattern of GRP94 and GRP78 was similar. There was a significant overexpression of GRP94 and GRP78 at both mRNA and protein levels in cancer tissues as compared to normal tissues. The relative levels of GRP94 and GRP78 mRNA evaluated by RT-PCR in cancer and normal lung tissue were: GRP94: 3.48+/-2.06 versus 2.01+/-1.83; GRP78: 3.64+/-1.87 versus 2.21+/-1.54; by real-time PCR were: GRP94: 2.89+/-0.64 versus 1.12+/-0.54; GRP78: 2.56+/-0.82 versus 0.96+/-0.42. The relative level of GRP94 and GRP78 protein by Western blot in cancer and normal lung tissue were: GRP94: 3.46+/-1.72 versus 1.81+/-0.92; GRP78: 4.84+/-2.55 versus 1.91+/-1.15, indicating an approximate 2-fold and a 3-fold increase in GRP94 and GRP78 protein in cancer tissue as compared with normal tissue. Immunohistochemistry result for GRP94 and GRP78 in cancer and normal tissue was similar, that is: a stronger stain was observed in cancer tissue (main intensity of staining ++ to +++) compared to normal tissue (main intensity of staining + to ++). All the difference for GRP94 and GRP78 between the two tissues were significant (p<0.05). Furthermore, the overexpression of GRP94 and GRP78 in the cancer tissue correlated with grade of differentiation and stage of tumors. There was stronger expression in poorly differentiated tumors than in well-moderately differentiated tumors (p<0.05). There was also stronger expression in stage III than in stages I and II tumors (p<0.05). No statistically significant differences were found among various pathologic types of tumors. Correlation analysis showed that there is a positive correlation between GRP94 and GRP78. CONCLUSION: The expression pattern of GRP94 and GRP78 was similar in human lung cancer. They both were related with the differentiation and progression of the cancer. The expression at mRNA and protein level may be valuable in evaluating the grade of differentiation and clinical stage of human lung cancer.     

NOB1 in Non-small-cell Lung Cancer: Expression Profile and Clinical Significance

Nin one binding (NOB1) gene has been reported up-regulated in several types of cancer. The aim of this study was to investigate the expression profile of NOB1 in non-small-cell lung cancer (NSCLC) and assess the clinical significance. qRT-PCR was used in the detection of NOB1 mRNA expression both in NSCLC tissue and in adjacent normal lung tissue. Western blot analysis and immunohistochemistry were used in the detection of NOB1 protein expression. The clinicopathological implications of NOB1 were analyzed statistically. It was confirmed by RT-qPCR that expression of NOB1 mRNA in NSCLC cells was higher than in human lung cells (P?<?0.05), and NOB1 mRNA was also over-expressed in NSCLC tissue when compared with adjacent tissue and normal lung tissue (P?<?0.05). Western blot analysis showed that NOB1 protein was significant increased in NSCLC cell lines compared with human lung cell line. Western blot analysis and immunohistochemistry showed that NOB1 protein was significant increased in NSCLC tissue compared with adjacent tissue and normal lung tissue (P?<?0.05). There were significant associations between NOB1 expression and TNM stage, lymph node metastasis, and histopathological grade (P?<?0.05), but not gender, age, smoke, or tumor diameter (P?>?0.05). Our results suggest that enhanced expression of NOB1 gene plays an important role in the occurrence and development of NSCLC. NOB1 may be a potential therapeutic target in NSCLC.     

柯萨奇病毒腺病毒受体在非小细胞肺癌中的表达及其意义

目的 研究柯萨奇病毒腺病毒受体(CAR)的mRNA和蛋白在正常肺组织、癌旁组织及肺癌组织中的表达情况,分析其与肺癌发生发展的相关性及在不同临床病理参数间的表达差异.方法 应用半定量逆转录聚合酶链反应(RT-PCR)方法和Western blot检测正常肺组织、癌旁组织和肺癌组织中CAR mRNA和CAR蛋白的表达情况.结果 CAR mRNA和蛋白在正常肺组织、癌旁组织和肺癌组织中的表达最分别为1.000±0.012、1.048±0.035、1.282±0.072和0.902±0.038、0.944±0.042、1.08±0.052,其差异均有统计学意义(P<0.05).CAR mRNA和CAR蛋白在肺癌中的表达呈正相关(r=0.448,P=0.026).在不同的临床病理参数之间,CAR mRNA和蛋白的表达在患者性别、年龄、吸烟与否、肿瘤大小、有无淋巴结转移及TNM分期中差异无统计学意义(P>0.05);CAR的表达在不同的病理类型中差异具有统计学意义(P=0.012),在7例细支气管肺泡痛(BAC)中均高表达(P=0.029).结论 肺癌组织中CAR的表达水平显著高于正常肺组织和癌旁组织,且在不同病理类型的表达上存在差异,提示CAR在肺癌的发生发展过程中起到了重要作用,并可能成为潜在的肿瘤标记及预后指标.     

Brevican,Neurocan, Tenascin-C and Versican are Mainly Responsible for the Invasiveness of Low-Grade Astrocytoma

The extent of tumor removal determines the effectiveness of postoperative oncotherapy. This is especially true for primary brain tumors, where peritumoral invasion usually makes radical resection impossible. The aim of the study was to determinate the specific expression pattern of invasion related molecules of different intracranial tumors and to identify molecules that are principally responsible for the peritumoral invasiveness of grade II astrocytoma mRNA expression of 26 extracellular matrix (ECM) molecules was determined in tissue samples from grade II astrocytoma, schwannoma, intracerebral metastases of non-small cell lung cancer and normal brain. Immunohistochemical staining for brevican, neurocan, tenascin-C and versican was also performed for each tumor group. Comparing astrocytoma to metastasis, schwannoma and normal brain; and metastasis and schwannoma to normal brain, 22, 17, 20, 21, and 19 molecules, respectively, were found to be significantly overexpressed at the mRNA level. Cluster analysis of mRNA expression showed a specific gene expression pattern for each histological group. Four molecules of 26 were found to be associated to astrocytoma. Immunohistochemical staining confirmed the results of the mRNA analysis at the protein level. Tumors of different origin have a specific invasive phenotype that can evidently determinate on gene expression level. This characteristic expression pattern of the invasion-related molecules might help to screen exact targets for anti-invasion drugs. In case of low-grade astrocytoma. brevican, neurocan, tenascin-C and versican were found to correlate principally with the invasive phenotype of low-grade astrocytoma, thus these molecules can potentially serve as targets for anti-invasion therapy in the future.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.     

EYA2在非小细胞肺癌中的表达

目的 探讨EYA2在非小细胞肺癌(NSCLC)中的表达及其与临床参数之间的关系.方法 59例NSCLC组织及癌旁正常肺组织,分别行Western blot分析及免疫组织化学染色,比较癌组织与肺组织之间EYA2表达差异,分析EYA2表达与肺癌临床参数之间的关系.结果 EYA2在NSCLC组织中的表达水平升高.EYA2分布于NSCLC细胞浆及细胞核中,胞浆中表达更明显.EYA2的表达与NSCLC病理类型有关,与分化程度、TNM分期、淋巴结转移等因素无关.EYA2在肺腺癌中表达明显升高,而在鳞癌中无变化.结论 EYA2在肺腺癌中表达水平升高,可能作为转录激活因子参与肺腺癌的发生、发展.