Expression of Heat Shock Protein 70 and 27 in Non-small Cell Lung Cancer and Its Clinical Significance

The heat shock proteins （HSPs） 70 and HSP 27 expression in patients with non-small cell lung cancer （NSCLC） was studied and the relation.ship between HSP 70 and HSP 27 with the clinicopathological features of NSCLC was investigated. The expression of HSP 70 and HSP 27 was detected in tumor tissues from 60 patients with NSCLC by S-P immunohistochemistry. The findings were analyzed in combination with the histological types, histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history and gender. The results showed that of the 60 NSCLC tissue specimens studied, the immunoreactivity of HSP 70 and HSP 27 was detected in 47 （78.3 %） and 43 （71.7 %） specimens, respectively. A positive correlation was found between the overexpression of HSP 70 and HSP 27. The histopathological differentiation, lymph node metastasis, clinical stages and smoking history were correlated to the expression of HSP 70, but not to the expression of HSP 27. No statistical significance was observed in histological types and gender with respect to both HSP 70 and HSP 27 expression. It is suggested that the HSP 70 expression is a powerful and significant prognostic indicator and is related to histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history, whereas HSP 27 expression is not.     

Reduced expression of PTEN protein and its prognostic significance in the gastrointestinal stromal tumor

Little is reported about the role of PTEN gene in the progression and prognosis of GISTs. This study examined the clinical implications of the tumor suppressor gene PTEN as a prognostic factor in the GISTs. Immunohistological staining and immunoblotting were employed to examine the PTEN protein expression, and its association with clinical measures. Clinicopathological features were reviewed by a retrospective examination of medical records. Reduced PTEN expression was significantly associated with tumor diameter, mitotic figure count, metastasis and pathological stage of tumor （P〈0.05）, and was not correlated with age, gender and tumor location （P〉0.05）. The 3-year survival rate of the patients with reduced PTEN expression was significantly lower than those with high PTEN expression （P〈0.01）. These results suggest that the expression of PTEN gene was significantly linked with the progression and metastasis of GISTs and it is an independent prognostic factor.     

Change of CMTM7 expression, a potential tumor suppressor, is associated with poor clinical outcome in human non-small cell lung cancer

Background CKLF-like MARVEL transmembrane domain-containing 7 （CMTM7） located at 3p22.3,is a frequent deletion site and a tumor suppressor gene （TSG） locus in many cancer,which suggests CMTM7 may be a potential TSG.The aim of this study was to investigate the correlations of CMTM7 expression and survival rate in patients with non-small-cell lung cancer （NSCLC）.Methods Surgical specimens of 180 cases with pathologically confirmed NSCLC were grouped into 18 tissue microarray slides.CMTM7 expression in these specimens were detected by immunohistochemistry staining and representative cases were confirmed by Western blotting.Univariate and multivariate analyses were performed to identify the association of CMTM7 expression with pathological features and survival of patients with NSCLC.Results A total of 78.9％ of the 180 patients had variations of CMTM7 protein expression,either up-regulated or downregulated.Univariate analysis showed that the patients＇ survival rate after surgery was highly correlated with CMTM7 expression （P=0.0091）.In addition,prognostic factors were examined by multivariate Cox regression analysis,and results suggested that CMTM7 expression was a unique prognostic factor in NSCLC survival.Conclusions The CMTM7 expression may be related to survival of patients with NSCLC and a unique prognostic factor.CMTM7 may play an important role in NSCLC development.     

Overexpression of glucosylceramide synthase and its significance in the clinical outcome of non-small cell lung cancer

Background Glucosylceramide synthase （GCS）,an enzyme responsible for ceramide glycosylation,plays an important role in multidrug resistance （MDR） in some tumors in vitro; however,its expression and clinicopathological significance in non-small cell lung cancer （NSCLC） remains unclear.Methods We evaluated GCS expression in 116 paired tumor and adjacent non-cancerous tissues and 50 frozen tissues from patients with NSCLC using immunohistochemistry and western blotting,and explored the correlation between GCS and NSCLC clinicopathological characteristics and prognosis.We observed the association between GCS and the MDR proteins P-glycoprotein （P-gp） and lung resistance-related protein （LRP） to determine the link between GCS and MDR at the histological level.Results GCS expression was significantly upregulated in NSCLC tumors compared with non-cancerous tissue.There was high GCS expression in 75/116 tumor specimens （64.7％） and 16/116 non-cancerous specimens （13.8％）.High GCS expression was significantly associated with poor differentiation （P=0.01）,lymph node metastasis （P=0.004）,recurrence/ distant metastasis （P=0.006）,and chemotherapy resistance （P=0.025）.Multivariate analysis demonstrated that GCS immunopositivity was an independent risk factor for survival （P=0.018）.P-gp was expressed in 80/116 tumors （69.0％） and in 12/116 non-cancerous tissue specimens （10.3％; P=0.001）; LRP was expressed in 85/116 tumors （73.3％） and 19/116 non-cancerous tissue specimens （16.4％; P=0.001）.Importantly,the results demonstrated that increased GCS expression in NSCLC cancer specimens correlated with increased expression of P-gp and LRP,molecules known to stimulate cancer cell MDR （r=0.612 and 0.503,P=0.01 and 0.035,respectively）.Conclusion GCS upregulation might contribute to the development of NSCLC and could be a useful prognostic indicator and chemoresistance predictor for NSCLC patients.     

Expressions of farnesoid X receptor and myeloid cell leukemia sequence 1 protein are associated with poor prognosis in patients with gallbladder cancer

Background Farnesoid X receptor （FXR） regulates tumorigenesis, but its clinical significance in gallbladder cancer （GBC） remains unclear. This study investigated its clinical and prognostic significance in GBC patients, as well as its association with the anti-apoptotic protein, myeloid cell leukemia sequence 1 （MCL1） protein. Methods FXR and MCL1 expression in 42 primary GBC and 15 normal gallbladder tissues were analyzed by immunohistochemistry. The patients and samples were collected from Ren Ji Hospital from January 2005 to December 2010. Their association with clinicopathologic factors and prognosis, as well as the correlation between FXR and MCL1 protein expression were analyzed by statistical analyses. Results Compared with normal gallbladder tissues, FXR expression was decreased and MCL1 expression was increased in GBC, during progression of tumor node metastasis （TNM） stage. The Kaplan-Meier survival analysis showed that FXR low-expression and MCL1 over-expression were significantly associated with overall poor survival. Furthermore, multivariate analysis showed that FXR and MCL1 are both prognostic factors for GBC patients. FXR low-expression was significantly correlated with MCL1 over-expression. Conclusion FXR might be a new molecular marker to predict the prognosis of patients with GBC and a novel therapeutic target. Chin Med J 2014;127 （14）： 2637-2642     

Investigation of tumor necrosis factor receptor-p55 expression in human colorectal cancer

Objective: To investigate the clinical significance of tumor necrosis factor receptor-p55 (TNFR-p55) expression and its relationship with the clinical pathology and Dukes‘ classification of human colorectal cancer. Methods: SABC immunohistochemistry method was used to examine TNFR-p55 expression in 91 specimens of colorectal cancer, 81 surrounding mucosas of the tumors and 13 normal tissues. Results: TNFR-p55 expression in colorectal cancer was significantly higher than that in the surrounding mucosa andnormal tissues, and it was significantly higher in the surrounding mucosa than in normal tissue. TNFR-p55 was inversely correlated to serous membrane invasion and lymph node metastasis of colorectal cancers.TNFR-p55 expression in Dukes‘ A and B stages was significantly higher than that of C stage. Conclusion: TNFR-p55 expression was important to determine the degree of malignancy and assess invasion depth, lymph node metastasis and Dukes‘ classification in colorectal cancer.     

Expression of maspin in non-small cell lung cancer and its relationship to vasculogenic mimicry

Maspin belongs to the serine protease inhibitor (serpin) family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the expression of maspin in non-small cell lung cancer (NSCLC) and its relationship to vasculogenic mimicry (VM). A total of 160 specimens of NSCLC were involved in this study and 20 specimens of normal lung tissue served as controls. VM, microvessel density (MVD) and the expression of maspin were detected by using immunohistochemical staining. The results showed that the positive rates of maspin and VM in the NSCLC group were 48.1% (77/160) and 36.9% (59/160), respectively, which were significantly different from those in the control group with the positive rates of maspin and VM being 100% and 0% respectively (P<0.05). VM, MVD and the expression level of maspin were significantly related to tumor differentiation, lymph node metastasis, clinical stages and postoperative survival time (all P<0.05). The maspin expression in patients with squamous cell carcinoma was significantly higher than that in those with adenocarcinoma (P<0.05). The maspin expression was negatively correlated with VM and MVD, and there was a positive correlation between VM and MVD. Maspin-negative expression, VM and high MVD score were negatively related to the 5-year-survival rate. PTNM stages, VM, MVD and maspin expression were independent prognostic factors for NSCLC (P<0.05). It was suggested that the loss of expression of maspin may participate in the invasion and metastasis of NSCLC and it has a positive relationship to VM in NSCLC. Combined detection of maspin, VM and MVD may help predict the progression and prognosis of NSCLC.     

Expression and Prognostic Significance of Livin in the Progression of Bladder Cancer

It has been suggested that progression of bladder transitional cell cancer (BTCC) may be regulated at the molecular level by a typical pattern of expression of genes involved in apoptosis. Re-cently Livin, belonging to the inhibitors of apoptosis (IAP) family, has been found to be expressed in most solid tumors, where its expression is suggested to have clinical significance. In order to explore the significance of Livin expression in the development of BTCC, immunohistochemistry and RT-QPCR were used to detect the expression of Livin mRNA in tumor tissues and adjacent normal tissues of 30 cases of BTCC. The results showed that the positive rate of Livin expression in adjacent normal tissues and tumor tissues was 0 and 60% (18/30) respectively. The -△△CT value of Livin in BTCC tissues was 8.0454 (7.4264-8.6644) times of that in adjacent normal tissues. The expression of Livin mRNA had no correlation with tumor pathological grades and clinical stages. It was sug-gested that there was weak expression of Livin mRNA in adjacent normal tissues, but strong in tumor tissues.     

Over-expression of small ubiquitin-like modifier proteases 1 predicts chemo-sensitivity and poor survival in non-small cell lung cancer

Background Non-small cell lung cancer （NSCLC） is one of the most common malignant tumors.Despite the advances in therapy over the years,its mortality remains high.The aim of this study was to evaluate the expression of small ubiquitin-like modifier （SUMO） proteases 1 （SENP1） in NSCLC tissues and its role in the regulation of vascular endothelial growth factor （VEGF） expression.We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.Methods A SENP1 small interfering RNA （siRNA） was constructed and transfected into the NSCLC cells.VEGF gene expression was analyzed by real-time polymerase chain reaction （RT-PCR）.Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.Results VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues.Inhibition of SENP1 by siRNA was associated with decreased VEGF expression.SENP1 was over-expressed in 55 of the 100 NSCLC samples （55％） and was associated with a moderate and low histological tumor grade （3.6％,38.2％,and 58.2％ in high,moderate and low differentiated tumors,respectively,P=0.046）,higher T stage （10.9％ in T1,and 89.1％ in T2 and T3 tumor samples,P ＜0.001）and TNM stage （10.9％ in stage Ⅰ,and 89.1％ in stages Ⅱ and Ⅲ tumor samples,P ＜0.001）.The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group （76.4％） than that in the SENP1 low expression group （33.3％,P ＜0.001）.Sixty three patients received postoperative chemotherapy,including 34 with SENP1 over-expression and 29 with SENP1 low expression.Among the 34 patients with SENP1 over-expression,22 （64.7％） patients developed recurrence or metastasis,significantly higher than those in the low expression group 27.6％ （8/29） （P=0.005）.Multivariate Cox regression analysis showed     

XAGE-1b基因在非小细胞肺癌中的表达及与临床特点的相关性研究

目的 探讨XAGE-1b基因在非小细胞肺癌中的表达水平及与临床特点的相关性.方法 非小细胞肺癌患者30例,通过手术获得肺癌组织和癌旁正常肺组织,分别提取组织总RNA,RT-PCR反应扩增XAGE-1b基因全长,通过电泳和基因测序鉴定RT-PCR产物,确定基因表达阳性标本,分析基因表达阳性率及与临床特征相关性.结果 30例肺癌组织中,XAGE-1b基因表达阳性率为40%(12/30),30例癌旁正常肺组织不表达该基因;基因表达与患者年龄、性别、肿瘤分化程度无相关性,与病理类型有相关性,腺癌中基因表达阳性率明显高于其他病理类型(61.1%vs 8.3%,p=0.015);随着TNM分期的升高,基因表达阳性率略有增加,但差异无统计学意义(P＞0.05).结论 XAGE-1b基因在肺腺癌中高表达,可优先选择该基因作为肺腺癌免疫治疗靶点.     

大肠癌中Pokemon的表达及其临床意义

目的:探讨原癌基因Pokemon(POK erythroid myeloid ontogenic)在大肠癌组织中的表达及其与临床特征之间的关系.方法:采用逆转录酶聚合酶链反应(RT-PCR)方法检测47例大肠癌患者癌、癌旁组织、癌以远大肠组织中Pokemon mRNA的表达水平,分析其与临床特征之间的关系;采用免疫组化ABC法检测53例大肠癌组织中Pokemon蛋白的表达,结合随访资料分析其与患者生存时间的关系.结果:大肠癌癌组织和癌旁组织中Pokemon mRNA水平显著高于正常大肠组织(P<0.05),而癌与癌旁组织中的表达无显著性差异;Pokemon mRNA的表达水平与大肠癌Dukes分期、分化程度及淋巴结转移相关(P<0.05),而与患者的性别、年龄、吸烟、饮酒、肿瘤位置、大小及浸润深度无关;Pokemon表达阴性的大肠癌患者存活率明显高于阳性表达患者(P<0.05).结论:Poke-mon在大肠癌和癌旁组织中高表达,并对大肠癌的预后评价有重要意义,且可能成为大肠癌治疗中有效的新的靶基因.     

抑癌基因PTEN在非小细胞肺癌中的表达及意义

目的研究抑癌基因VFEN（phosphatase and tensin homolog deleted from chromosome 10；10号染色体缺失与张力蛋白同源物磷酸酯酶基因）在非小细胞肺癌中的表达及与非小细胞肺癌临床病理特征的关系及意义。方法采用免疫组织化学染色方法（PV-6000通用型二步法）检测62例NSCLC组织和20例癌旁肺组织中VFEN蛋白表达。结果VFEN蛋白表达在NSCLC为50％（31／62），明显低于癌旁肺组织90％（18／20），差异有统计学意义（P〈0．05）。FFEN蛋白表达与NSCLC细胞分化程度、TNM分期和淋巴结转移有关，差异有统计学意义（P〈0．05）。结论VFEN蛋白低表达与NSCLC的发生、细胞增殖、浸润和淋巴结转移相关，可望作为预后观测的指标和分子治疗的新靶点。     

Nucleostemin基因及PCNA在非小细胞肺癌组织中的检测及意义

目的：探讨Nucleostemin基因及PCNA在非小细胞肺癌（NSCLC）组织中的检测及意义。方法：采用免疫组织化学sP法对53例NSCLC患者的非小细胞肺癌组织和15例癌旁正常者的组织中NS蛋白进行检测,并对其与NSCLC患者临床病理特征关系进行分析。结果：NS蛋白在NSCLC中的表达率为54．7％（29／53）明显高于癌旁正常组织中的表达率0（0／15）,NS蛋白腺癌组织的表达率为65．2％（15／23）明显高于鳞癌组织的表达率46．7％（14／30）,高、中分化组织的表达率42．9％（15／35）明显低于低分化组织的表达率77．8％（14／18）,比较差异均有统计学意义（P〈0．05）,与患者TNM分期及淋巴结转移无关（P〉0．05oNSCLC组织中PCNA阳性率71．7％（38／53）明显高于癌旁正常组织6．7％（1／15）,差异有统计学意义（P〈0．05）。结论：NSCLC患者非小细胞肺癌组织中,NS基因mRNA和蛋白存在明显的高表达趋势,PCNA阳性率显著增高,有利于肿瘤细胞恶性增殖,因而是一种临床应用价值较高的肿瘤分子标志物。     

Merlin蛋白在非小细胞肺癌中的表达及临床意义

目的:研究Merlin蛋白在非小细胞肺癌中的表达及临床意义.方法:免疫组织化学法测定45例非小细胞肺癌组织、癌旁组织、正常组织的Merlin蛋白的表达,并对癌组织中的表达与其组织学分型、性别、P-TNM分期、分化程度及淋巴结转移情况等因素进行分析.结果:Merlin蛋白在正常组织及肺癌组织中阳性率分别为15.56%和7...     

非小细胞肺癌VEGFR-2的表达及临床意义

目的:探讨血管内皮生长因子受体-2(vascular endothelial growth factor receptor 2,VEGFR-2)在非小细胞肺癌(non-small-cell lung cancer,NSCLC)中的表达及其与临床病理特征?预后的关系?方法:采用组织芯片技术和免疫组织化学方法检测VEGFR-2在217例非小细胞肺癌中的表达情况,并结合临床病理资料进行单因素生存分析?结果:VEGFR-2在NSCLC中高表达,阳性率为63.1%,且该基因的表达与肿瘤分化程度?TNM分期?淋巴结转移?神经侵袭有显著相关性(P < 0.05)?VEGFR-2的表达与NSCLC的预后相关,阳性表达该基因的患者的平均中位生存期比阴性表达的患者长12个月(P=0.049)?结论:VEGFR-2基因在非小细胞肺癌的发生?发展过程及预后具有重要作用?     

金属蛋白酶诱导因子CD147在非小细胞肺癌中的表达及其意义

目的 探讨细胞外基质金属蛋白酶诱导因子CD147在非小细胞肺癌中的表达及其临床意义.方法 采用免疫组织化学方法和逆转录聚合酶链反应检测57例人非小细胞肺癌及其相应癌旁正常组织中CD147蛋白表达及mRNA水平,并分析CD147蛋白表达与非小细胞肺癌临床病理特征的关系.结果 CD147蛋白及mRNA在人非小细胞肺癌组织中的阳性率均明显高于癌旁正常组织,且在非小细胞肺癌中CD147蛋白表达与年龄、性别及病理组织学分型无关(P>0.05),与淋巴结转移及TNM分期相关(P<0.05).结论 CD147表达可能与非小细胞肺癌侵袭和转移密切相关,可作为评价非小细胞肺癌恶性程度的重要指标之一.     

85例非小细胞肺癌中p53基因异常的预后价值

目的：探讨ｐ５３蛋白表达和基因突变在非小细胞肺癌（ＮＳＣＬＣ）中的预后价值。方法：利用免疫组化方法检测８５例ＮＳＣＬＣ的ｐ５３蛋白表达，聚合酶链式反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）方法检测３１例肺腺癌ｐ５３基因５、６、７、８外显子突变，研究结果进行单因素生存分析。结果：本组ＮＳＣＬＣ病人的平均年龄为５５．６±８．４岁（中位数５５岁），随访时间的中位数为４７个月，３年、５年总体生存率分别为６６％和６１％。ｐ５３蛋白表达与预后无关（χ２＝１．００，Ｐ＝０．８），而ｐ５３基因突变组病人的生存率显著低于无ｐ５３基因突变组（χ２＝４．８１，Ｐ＝０．０３）。同时，ｐ５３蛋白表达与ＰＣＲ－ＳＣＰ检测的ｐ５３基因突变的一致率仅为５２％。结论：在ＮＳＣＬＣ中ｐ５３蛋白表达和基因突变可能有不同的预后意义，ｐ５３基因突变可作为肺腺癌的辅助预后指标。     

非小细胞肺癌组织中ERCC1基因的表达及临床意义

目的 探讨非小细胞肺癌(NSCLC)组织ERCC1基因mRNA表达情况及其临床意义.方法 采用反转录-聚合酶链反应(RT-PCR)方法检测82例肺癌组织、36例癌旁组织及15例良性组织中ERCC1基因mRNA的表达情况.结果 ERCC1基因在NSCLC患者癌、癌旁及良性组织中均有表达,分别为54.9%(45/82)、4...