Expressions of Livin and Smac proteins in non-small cell lung cancer

Objectlve:To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase(Smac) proteins in non-small cell lung cancer(NSCLC),and analyze their effect on patients'prognosis.Methods:The expressions of Livin and Smac proteins were detected in 89 NSCLC tissue samples and 25 normal lung tissue samples by immunohistochemical technique.Results:The positive expression rates of Livin and Smac proteins in NSCLC tissues were 53.9%.and 58.4%respectively,higher than that in normal lung tissues(P＜0.01).Livin protein expression correlated with Smac protein significantly(χ2=18.451,P=0.000,r=0.455).The expression level of Livin protein was closely related to lymph node metastasis,TNM stage and histological type(P＜0.05),but not to sex,age,differentiation grade(P＞0.05).The expression level of Smac protein was closely related to lymph node metastasis,TNM stage(P＜0.01),but not to sex,age,histological types(P＞0.05).Kaplan-Meier analysis revealed a significant impact on survival by Livin protein in NSCLC (P＜0.01),but not by Smac protein(P＞0.05).Conclusion:Overexpression of Livin protein may play a promoting role in the occurrence and progression of NSCLC.Moreover,it may bring an adverse effect on patients'prognosis.Although overexpression of Smac protein affects the occurrence and progression of NSCLC,it has no relationship with the prognosis.Livin protein may be helpful to evaluate the progression of NSCLC,and to predict the prognosis.     

Expression of MMP-13 and its correlation with prognosis in non-small cell-lung cancer

Objective： To investigate the expression of MMP-13 in non-small cell lung cancer （NSCLC）, so as to analyze its correlation with prognosis of NSCLC. Methods： MMP-13 expression was detected in 99 NSCLC tissues and 32 normal lung tissues by immunohistochemical method. Results： （1） Expression of MMP-13 （51.5%, 51/99） in cancer tissues was significantly higher than that in normal tissues 0% （P 〈 0.05）. Expression level of MMP-13 was significantly related to lymph node metastasis and clinical stage （P 〈 0.01）. （2） Kaplan-Meier analysis showed that expression level of MMP-13 was closely cor- relate with the prognosis of NSCLC. Multivariate Cox model analysis suggested that the survival time was significantly related to clinical stage and the expression of MMP-13. Conclusion： MMP-13 is an independent factor that affect prognosis.     

Detection of Brk expression in non-small cell lung cancer: clinicopathological relevance

Breast tumor kinase (Brk), also known as protein tyrosine kinase 6, is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk upregulation and oncogenic properties have been found in several malignant tumors, including breast, colon carcinomas, and melanomas, but the expression of Brk and its clinical significance in non-small cell lung cancer (NSCLC) remains unclear. In the current study, we examined the expression of Brk and its correlation with clinicopathological features involving p53, ki67, and E-cadherin status in NSCLC tissue using immunohistochemistry. We also used immunocytochemistry and immunofluorescent staining to examine the Brk expression and its subcellular localization in NSCLC cell lines, including LTE and H460. We further confirmed cytoplasmic and nucleus expression of Brk in LTE and H460 cells using Western blotting. The Brk expression in NSCLC cells was mainly found in cytoplasm (59/122, 48.4%) with some nucleus staining (17/122, 13.9%) with a total positive rate of 53.3% (65/122). Cytoplasmic Brk expression in NSCLC was higher than that in normal lung tissues (24/122, 19.7%) (P < 0.05). Increased cytoplasmic Brk expression in NSCLC was associated with large tumor size (≥3 cm), lymph node metastasis, and advanced tumor–node–metastasis (TNM) stages (III and IV) (P < 0.05). Moreover, increased cytoplasmic Brk expression was positively associated with Ki67 status in NSCLC (P < 0.05). Reduced E-cadherin expression was also found to be associated with lymph node metastasis and advanced TNM stages (III and IV) in NSCLC (P < 0.05). Brk expression was not associated with E-cadherin expression and P53 status in NSCLC (P > 0.05). The present findings indicate an increase of cytoplasmic Brk expression in NSCLC which may play a role in tumor development, including tumor expansion and lymph node metastasis in which Ki67, but not E-cadherin, and P53 status may be involved.     

P53、C-erbB-2和VEGF在非小细胞肺癌中的表达及其临床意义

Objective: To investigate the expressions and the clinical significance of P53, C-erbB-2 and vascular endothelial growth factor(VEGF)in non-small cell lung cancer(NSCLC).Methods: 121 specimens of NSCLC were examined for P53, C-erbB-2 and VEGF by immunohistochemical staining.Results: The positive rates of P53, C-erbB-2 and VEGF in the carcinomatous tissue were 43%, 39% and 31% respectively.P53 gene protein expression in lung cancer was significantly related to histological type and P-TNM staging of lung cancer patients(P＜0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and cell differentiation(P＞0.05).C-erbB-2 gene protein expression in lung cancer was closely related to histological type and cell differentiation(P＜0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and P-TNM staging of lung cancer patients(P＞0.05).VEGF in lung cancer was only closely related to cell differentiation(P＜0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis, histological type and P-TNM staging of lung cancer patients(P＞0.05).Conclusion: It is possible for P53, C-erbB-2 and VEGF to play an important role in the oncogenesis and development of non-small cell lung cancer.     

Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer

Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.     

Increased NDRG1 Expression is Associated with Advanced T Stages and Poor Vascularization in Non-small Cell Lung Cancer

N-myc downstream regulated gene 1 (NDRG1) is a member of the N-myc downstream regulated gene family which belongs to the alpha/beta hydrolase superfamily. Earlier studies have shown its association with inhibition of tumor metastasis. However, its function in malignant tumors is not fully enunciated. Recently there was increasing evidence that NDRG1 is involved in stress responses. In the current study, we examined the expression of NDRG1 and its correlation with clinicopathological factors and microvessel density (MVD) in non-small cell lung cancer (NSCLC) using immunohistochemistry (IHC). NDRG1 expression in NSCLC (71/115, 61.7%) was higher than that in normal lung tissues (32/115, 27.8%) (p < 0.05). NDRG1 expression in NSCLC cells was found in cytoplasm (63/115, 54.8%), nuclear (24/115, 20.9%) and cell membrane (13/115, 11.3%). NDRG1 expression in NSCLC with advanced T stages (T2-4) (63/84, 75.0%) was significantly higher than that with T1 stage (8/31, 25.8%) (P < 0.05). No other clinicopathological factors including lymph node metastasis were found to be associated with NDRG1 expression (p > 0.05). Moreover increased NDRG1 expression was associated with lower MVD in NSCLC (P < 0.05). MVD in adenocarcinoma (33.4 ± 8.4/HP) was significantly higher than that in squamous cell carcinoma (SCC) (19.3 ± 8.1/HP) (P < 0.05). No other clinicopathological factors were associated with MVD in NSCLC (p > 0.05). The present findings indicate an increase of NDRG1 expression with the progress of tumour extent which may be due to unbalanced tumor oxygenation on account of poor vascularization in NSCLC.     

Expression of GPC3 protein and its significance in lung squamous cell carcinoma

The purpose of this study was to investigate GPC3 gene expression in lung squamous cell carcinoma tissue and its correlation with clinical and tumor characteristics. Using RT–PCR, the presence of GPC3 gene expression was detected in cancer tissue and adjacent normal tissue in 66 cases of lung squamous cell carcinoma and positive rates were calculated. Using Western blot, changes in GPC3 protein expression were detected in lung squamous cell carcinoma and adjacent normal tissues. The percentage of tissue samples expressing GPC3 mRNA was significantly higher in lung squamous cell carcinoma than in adjacent normal tissue (P < 0.05). This percentage was also significantly higher for cases with lymph node metastasis than for those without lymph node metastasis (P < 0.05). Further, the percentage of samples expressing GPC3 mRNA was higher with lowering degrees of tumor differentiation (P < 0.05). Rates of GPC3 expression were, however, independent of patient gender, age, and tumor size (P > 0.05). The expression of GPC3 protein in lung squamous cell carcinoma was significantly higher than that in adjacent normal tissues (P < 0.05). The expression in cases with lymph node metastasis was significantly higher than in those without lymph node metastasis (P < 0.05), and GPC3 protein expression increased with lowering degrees of tumor differentiation (P < 0.05). Further investigation is warranted for the association of initiation, development, invasion, and metastasis of disease.     

AKT1表达与非小细胞肺癌临床病理特征及预后的关系

目的探讨丝/苏氨酸蛋白激酶1(AKT1)表达与非小细胞肺癌(NSCLC)病理学特征及预后的关系。方法选取经病理学检查证实的NSCLC患者90例,分别取其癌组织、癌旁组织为NSCLC组和癌旁组,采用免疫组化染色法检测2组标本中的AKT1蛋白表达水平,并分析AKT1蛋白与NSCLC患者TNM分期、淋巴结转移情况、肿瘤分化程度、病灶的大小及预后等指标的关系。结果NSCLC组标本中的AKT1蛋白阳性表达率(58.89%)显著高于癌旁组(11.11%),差异具有统计学意义(P<0.05)。高分化及中分化、TNM分期(Ⅰ期+Ⅱ期)、未发生淋巴结转移的NSCLC组中AKT1蛋白阳性表达率低于低分化、TNM分期(Ⅲ期和Ⅳ期)及发生淋巴结发生转移NSCLC组织(P<0.05),不同年龄、性别、病灶大小及病理学类型的NSCLC组织中AKT1蛋白阳性表达率差异无统计学意义(P>0.05)。NSCLC组标本中的AKT1蛋白阳性表达与阴性表达患者的1年、2年生存率差异无统计学意义(P>0.05),AKT1蛋白阳性表达患者的3年生存率(13.21%)显著低于AKT1蛋白阴性表达患者的37.84%(P<0.05)。结论NSCLC患者癌组织中的AKT1蛋白表达上调,并且与肿瘤进展及不良预后关系密切。     

Survivin和Cox-2蛋白与非小细胞肺癌危险因素的系统评价

目的:系统评价存活蛋白(Survivin)、环氧化酶2(cyclooxygenase 2,Cox-2)表达水平与非小细胞肺癌non-small cell lungcancer,NSCLC)危险因素的关系。方法:计算机检索Cochrane Library(2011年第1期),PubMed、CNKI等数据库,并辅以手工检索,按照纳入与排除标准选择病例对照试验。评价质量及提取资料后,采用RevMan 4.2.10软件对数据库进行系统评价。结果:对于Survivin,共纳入15个研究,其中1 222例NSCLC患者,447例正常对照。Meta分析结果显示:Survivin在NSCLC组及正常对照组[比值比(odds ratio,OR)=11.11,95%可信区间(confidenceinterval,CI)为5.92～20.83]的表达差异具有统计学意义(P0.05)。临床病理检查结果显示:Survivin在TNM分期T3～T4期与T1～T2期,临床分期Ⅲ～Ⅳ期与Ⅰ～Ⅱ期,淋巴结转移组与非淋巴结转移组,低分化组与中高分化组间的表达差异均具有统计学意义(P均0.05)。对于Cox-2,共纳入12个研究,其中975例NSCLC患者,209例正常对照。Meta分析结果显示:Cox-2在NSCLC组及正常对照组(OR=29.46,95%CI=15.91～54.56)的表达差异具有统计学意义(P0.05)。临床病理检查结果显示:Cox-2在TNM分期T3～T4期与T1～T2期的表达差异无统计学意义(P0.05)。Cox-2在临床分期Ⅲ～Ⅳ期与Ⅰ～Ⅱ期,淋巴结转移组与非淋巴结转移组,低分化组与中高分化组间的表达差异均具有统计学意义(P均0.05)。Spearman等级相关分析显示,Survivin与Cox-2蛋白阳性率在NSCLC中的表达具有相关性(r=0.514,P0.05)。结论:Survivin、Cox-2在NSCLC中高表达,增加了其恶性行为的发生危险,同时Survivin与Cox-2在NSCLC表达也有一定的相关性。     

CD44V6在非小细胞肺癌中表达的研究

目的 研究CD44V6基因蛋白与非小细胞肺癌(NSCLC)临床病理特征的关系。方法 用S-P免疫组化检测74例NSCLC CD44V6基因蛋白的表达。结果 CD44V6总的阳性表达率为44.6％(33/74),阳性表达与淋巴结有无癌转移、PTNM分期显著相关(P<0.01),与患者3年生存期呈负相关(P<0.05),与细胞的分化程度、年龄、性别均未见显著相关(P>0.05)。结论 CD44V6过表达与NSCLC的预后有密切关系,可作为临床评估、预测肿瘤转移潜能和预后的指标。     

Expression and Significance of RKIP and E-cadherin in Lung Squamous Cell Carcinoma

The purpose of this study was to investigate the expression of Raf kinase inhibitor protein (RKIP) and epithelial cadherin (E-cadherin) in lung squamous cell carcinoma tissue and its correlation with the clinical pathology of lung squamous cell carcinoma. RKIP and E-cadherin mRNA (by RT-PCR) and protein (by western blotting) levels were monitored in carcinoma tissues and surrounding normal tissues from 86 lung squamous cell carcinoma cases, and their positive rates were calculated. The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P?<?0.05). The positive expression rates were significantly lower in those with lymph node metastasis than in those without (P?<?0.05). The lower the degree of tumor differentiation, the lower the E-cadherin mRNA positive expression rate (P?<?0.05). The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in patients at advanced (III, IV) stages than in patients at early (I, II) stages (p?<?0.05); this rate, however, was independent of gender, age, and tumor size (P?>?0.05). The protein levels of RKIP and E-cadherin were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P?<?0.05). The levels were significantly lower in patients with lymph node metastasis than in those without it (P?<?0.05). The lower the degree of tumor differentiation, the lower the protein level of E-cadherin (P?<?0.05). Both RKIP and E-cadherin are tumor suppressors, their low expression levels may be associated with initiation, invasion and/or metastasis, as well as with the inhibition of lung squamous cell carcinoma differentiation.     

Expression of p114RhoGEF predicts lymph node metastasis and poor survival of squamous-cell lung carcinoma patients

The Rho-specific guanine nucleotide exchanging factor p114RhoGEF is involved in RhoA activation and cell motility. Previous studies suggest that altered expression of p114RhoGEF could contribute to cancer progression. We investigated an association of p114RhoGEF expression with progression and prognosis of non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to detect p114RhoGEF expression in 105 NSCLC (34 adenocarcinoma and 71 squamous-cell carcinoma) and 32 normal lung tissues. We found that p114RhoGEF expression was upregulated in squamous-cell lung carcinoma and that p114RhoGEF expression was significantly higher in squamous-cell carcinoma than in adenocarcinoma or normal tissues (P?<?0.05, both). Expression of p114RhoGEF protein was significantly associated with lymph node metastasis of lung cancer (P?<?0.05), but not with patients’ age, gender, tumor size, differentiation, or stage. Expression of p114RhoGEF protein was also associated with poor overall and event-free survival of squamous-cell lung carcinoma patients (P?<?0.05). Taken together, p114RhoGEF expression may be useful in predicting progression and survival of squamous-cell lung carcinoma patients. A future study will investigate whether p114RhoGEF can serve as a novel therapeutic target in squamous-cell lung cancer.     

E-cadherin、CD44v6和PCNA在非小细胞肺癌组织中的表达及意义

背景与目的:上皮钙依赖粘附蛋白(E-cadherin,E-cad)、CD44v6和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在恶性肿瘤侵袭与转移中发挥重要作用。本研究旨在探讨E-cad、CD44v6和PCNA在非小细胞肺癌(non-small cell lung cancer,NSCLC)及癌旁组织中的表达与NSCLC的侵袭、转移及预后的关系。方法:应用免疫组化EnVision法检测86例NSCLC组织及40例癌旁组织中E-cad、CD44v6和PCNA的表达,并分析与NSCLC的侵袭、转移及预后的关系。结果:E-cad在肺癌组织中的表达率为53.5%(46/86),显著低于癌旁组织(80.0%)(P<0.05),且与NSCLC的分化程度、淋巴结转移和TNM分期有关(P<0.05);CD44v6在肺癌组织中的表达率为44.2%(38/86),在癌旁组织中无表达,且在鳞癌中的表达率(54.0%)显著高于腺癌(30.6%)(P<0.05),并且与淋巴结转移和TNM分期有关(P<0.05);PCNA在肺癌组织中的表达率为48.8%(42/86),在癌旁组织中无表达,且在淋巴结转移组与未转移组间的表达差异有统计学意义(P<0.05)。E-cad与PCNA的表达呈显著性负相关(r=-0.554,P<0.05),而CD44v6与PCNA的表达呈显著性正相关(r=0.688,P<0.05)。单因素生存分析显示E-cad、CD44v6及PCNA的表达与NSCLC患者预后有关。Cox比例风险模型进行多因素生存分析显示;E-cad与临床分期是有意义的预后指标(P<0.05)。结论:E-cad、CD44v6及PCNA的表达与NSCLC的侵袭和转移相关。在NSCLC中联合检测三者的表达对判断预后有参考价值。     

MACC1和c-met在非小细胞肺癌中的表达及其预后价值

背景与目的已有的研究表明结肠癌转移相关基因1(metastasis-associated in colon cancer1,MACC1)是一个与肿瘤浸润转移相关的新基因,该基因能够调节肝细胞生长因子受体(hepatocyte growth factor receptor,c-met)的表达。本研究旨在探讨MACC1和c-met在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其与浸润转移和预后的关系。方法采用免疫组化检测103例NSCLC组织及40例癌旁正常组织中MACC1和c-met蛋白的表达。结果 MACC1和c-met在NSCLC组中的阳性表达率均明显高于正常肺组织(P<0.001)。MACC1和c-met阳性率均与肺癌的分化程度、T分期、淋巴结转移和TNM分期相关(P<0.05),而与性别、年龄、吸烟及组织学类型等无关(P>0.05)。MACC1和c-met的表达呈正相关(r=0.403,P<0.001)。Kaplan-Meier生存曲线显示MACC1和c-met阳性组5年生存率均明显低于阴性组(P<0.05)。Cox多因素分析显示MACC1是NSCLC的独立预后因素(P=0.026)。结论 MACC1和c-met的表达与肺癌的分化、浸润和转移密切相关,两者均对生存期有一定的影响,MACC1是NSCLC的独立预后危险因素。     

OTUD1在非小细胞肺癌中的表达及其与临床病理特征的相关性

目的 探究OTUD1在非小细胞肺癌中的表达及其与临床病理特征的相关性.方法 选取在南阳市第二人民医院经病理确诊的70例非小细胞肺癌患者,采用免疫组织化学法检测肿瘤组织及癌旁组织中OTUD1表达情况,并分析其表达水平与临床病理特征的相关性.结果 肺癌组织的OTUD1高表达率为48.57％,显著高于正常组织的5.71％(P...     

NSCLC外周血循环肿瘤细胞水平检测及其与TNM分期、预后的关系

目的:分析非小细胞肺癌（non-small cell lung cancer,NSCLC）外周血循环肿瘤细胞（circulating tumor cells,CTC）表达特点及其与国际抗癌联盟肿瘤通用分期（tumor node metastasis,TNM）及预后的关系。方法:采集我院胸外科收治的NSCLC患者82例,选取肺良性疾病30例作为良性组及30名正常志愿者作为对照组,入院后均完成外周血CTC检测,比较NSCLC外周血CTC与良性组、对照组之间的差异;比较不同病理类型、TNM分期、不同预后NSCLC患者CTC阳性率,筛选NSCLC预后影响因素。结果:NSCLC组CTC阳性率高于良性组与对照组（P＜0.05）,良性组、对照组组间对比差异无统计学意义（P＞0.05）;不同病理类型NSCLC患者CTC阳性率比较差异无统计学意义（P＞0.05）;不同TNM分期NSCLC患者CTC阳性率比较差异有统计学意义（P＜0.05）,各分期CTC阳性率比较:Ⅲa期＞Ⅱ期＞Ⅰ期;CTC阴性NSCLC患者随访中位无 病生存时间（disease free survival,DFS）长于阳性组,复发、转移率低于阳性组（P＜0.05）;有吸烟史、CTC阳性、高TNM分期、伴淋巴结转移的NSCLC患者中位DFS低于无吸烟史、CTC阴性、低TNM分期、无淋巴结转移的NSCLC患者（P＜0.05）;Cox回归分析显示:TNM分期、CTC、淋巴结转移均为影响NSCLC患者中位DFS的相关因素（P＜0.05）。结论:NSCLC外周血CTC阳性率较高,且与TNM分期、淋巴结转移共同影响患者预后。     

Smac在Ⅰ～Ⅱ期非小细胞肺癌组织中的表达及其临床意义

背景与目的：Smac是新近发现的一种由线粒体释放的促凋亡蛋白,主要作用于凋亡抑制蛋白（inhibitor of apoptosis proteins）．促进凋亡的发生：Smac在体外实验中显示出抗肿瘤作用,但在肺癌中其作用尚不明确。本研究通过检测Smac蛋白在Ⅰ～Ⅱ期非小细胞肺癌的表达,探讨其与临床病理因素及预后的关系。方法：采用组织芯片和免疫组化方法,对213例Ⅰ、Ⅱ期非小细胞肺癌肿瘤组织中Smac蛋白的表达情况进行检测。结果：Ⅰ、Ⅱ期NSCLC的5年生存率分别为61．9％和30．0％。Smac蛋白主要定位于细胞浆,以75％的阳性细胞数为分界点时,低表达组占60．6％。高表达组占39．4％。Smac的表达与性别、年龄、血型、病理类型及生存无相关性（P〉0．05）,但Smac蛋白在无淋巴结转移和有淋巴结转移的表达分别为37．0％和58．3％．二者比较有统计学意义（P〈0．05）。结论：Smac蛋白与Ⅰ～Ⅱ期非小细胞肺癌的淋巴结转移有关。