ABCE1在人肺腺癌组织中的表达及其临床意义

ABCE1基因属ATP结合家族成员之一,其表达的ABCE1蛋白是一种高度保守的蛋白,在所有的真核及原核生物中都有1～2种转录本普遍表达.ABCE1蛋白能够特异性结合并抑制哺乳动物细胞内一种被干扰素诱导的核糖核酸酶L,因此又被称为核糖核酸酶L抑制因子.     

LKB1蛋白在肺腺癌组织中的表达及临床意义

目的：了解LKB1蛋白在肺腺癌组织中表达的临床意义.方法：应用免疫组化法检测62例肺腺癌组织中LKB1蛋白表达情况.结果：LKB1蛋白在肺腺癌细胞及正常肺支气管上皮均有表达,弥漫性分布于细胞质,细胞核亦有表达.肺腺癌组织中LKB1蛋白表达的阴性率为38.7%（24/62）.LKB1的表达与肺腺癌TNM分期中的淋巴结转移（N）及临床分期有显著的相关性,X^2=10.620,P=0.014;X^2=18.635,P=0.000.LKB1蛋白阴性组预后较差,中位生存期为15个月,而LKB1阳性组的中位生存时间为29个月,两者比较差异有统计学意义,X^2=1 5.350,P=0.000.结论：LKB1蛋白表达下降与肺腺癌发生淋巴结转移相关,是肺腺癌预后不良的风险因素之一.     

ASCL-1在肺腺癌组织中的表达及与预后相关性研究

  目的  ASCL-1基因表达与肺神经内分泌肿瘤(小细胞癌、非典型类癌、典型类癌、大细胞神经内分泌癌)密切相关。本研究旨在分析ASCL-1蛋白在肺腺癌组织中的表达情况及与预后的相关性。  方法  采用免疫组织化学法检测南京医科大学附属肿瘤医院2008年1月至2010年1月283例肺腺癌组织中ASCL-1、神经内分泌标志物嗜铬蛋白A (chromogranin A,CgA)、突触素(synaptophysin,Syn)和CD56的表达并进行对比分析,采用Western blot法检测对肺腺癌及癌旁组织中ASCL-1的表达进行检测。采用单因素χ2检验和Logistic多因素回归分析探究影响ASCL-1表达的相关因素,并采用Kaplan-Meier法对肺腺癌患者进行预后评估。  结果  ASCL-1在肺腺癌中的表达阳性率为16.9% (48/283),与神经内分泌标志物的表达呈正相关(0＜r＜1,P＜0.05)。采用Western blot法检测63例患者的肺腺癌组织,9例ASCL-1蛋白表达,而对应癌旁肺组织均无蛋白表达。经单因素χ2检验和多因素Logistic回归分析,发现ASCL-1的表达与肺腺癌患者的吸烟、肿瘤分化程度、TNM分期、淋巴结转移相关。经Kaplan-Meier生存分析显示,ASCL-1蛋白表达阳性组患者总生存期(overall survival,OS)低于阴性组。  结论  ASCL-1蛋白表达可能是肺腺癌患者预后的危险因素之一。      

LKB1蛋白在肺腺癌组织中的表达及临床意义

目的:了解LKB1蛋白在肺腺癌组织中表达的临床意义。方法:应用免疫组化法检测62例肺腺癌组织中LKB1蛋白表达情况。结果:LKB1蛋白在肺腺癌细胞及正常肺支气管上皮均有表达,弥漫性分布于细胞质,细胞核亦有表达。肺腺癌组织中LKB1蛋白表达的阴性率为38.7%(24/62)。LKB1的表达与肺腺癌TNM分期中的淋巴结转移(N)及临床分期有显著的相关性,χ2=10.620,P=0.014;χ2=18.635,P=0.000。LKB1蛋白阴性组预后较差,中位生存期为15个月,而LKB1阳性组的中位生存时间为29个月,两者比较差异有统计学意义,χ2=15.350,P=0.000。结论:LKB1蛋白表达下降与肺腺癌发生淋巴结转移相关,是肺腺癌预后不良的风险因素之一。     

Pim-3、MCM7蛋白在人肺腺癌组织中的表达及其临床意义

目的:探讨Pim-3和MCM7蛋白在人肺腺癌组织中的表达及其临床意义。方法:采用免疫组化En-Vision法检测30例人正常肺组织和60例人肺腺癌组织中Pim-3和MCM7蛋白的表达,分析二者与临床病理特征之间的关系。结果:60例肺腺癌组织中Pim-3和MCM7蛋白的阳性表达均显著高于正常组(P<0.001,P<0.001),肺腺癌组中Pim-3和MCM7蛋白的阳性表达均与原发肿瘤的大小、组织学分级、淋巴结转移及TNM分期有关(P<0.02),而与患者的年龄、性别无关(P>0.05)。Pim-3与MCM7蛋白的表达水平呈显著正相关(r=0.786,P<0.01)。结论:Pim-3和MCM7蛋白的协同表达可能涉及了肺腺癌的发生、发展过程,Pim-3激酶可能是肺腺癌分子靶向药物治疗的新靶标。     

肺腺癌和鳞癌组织中mdm2蛋白表达的临床研究

目的了解mdm2蛋白的表达与肺腺癌、鳞癌临床病理特征之间的关系及意义,探讨mdm2蛋白在肺癌发生、发展过程中的可能作用。方法用免疫组化法(SP法)检测mdm2蛋白在53例肺癌组织和19例癌旁正常肺组织的表达情况,并结合肺癌的临床病理特征进行对比分析。结果mdm2蛋白定位于细胞质或细胞核,为棕黄色颗粒。53例肺癌组织mdm2蛋白过表达率为52.8% (28/53),19例癌旁正常肺组织均不表达mdm2蛋白,二者差异有显著性(P<0.05)。Ⅲ～Ⅳ期和有淋巴结转移肺癌的mdm2蛋白过表达率分别为71.4%(15/21)和67.7%(21/31),显著高于Ⅰ～Ⅱ期(40.6%)和无淋巴结转移的过表达率(31.8%,P<0.05)。低分化肺癌mdm2蛋白过表达率90.0% (9/10)显著高于高分化及中分化的过表达率(40.0%和45.5%,P<0.05)。mdm2蛋白过表达率与患者年龄、性别、吸烟史及病理类型无显著相关性(P>0.05)。mdm2蛋白过表达组肺癌患者的术后5年生存率显著低于不表达组(P<0.05)。结论mdm2蛋白在肺癌中过表达与淋巴结转移、pTNM分期、分化程度有关。mdm2蛋白过表达可能在肺癌的发生、发展及预后中起重要作用。     

肺鳞癌组织中p27kip1的表达及其与临床预后因素的相关性

目的探讨p27kip1在肺鳞状细胞癌组织中的表达,及其与临床独立预后因素和生存率的关系,寻找基因治疗的依据。方法通过免疫组化检测48例肺鳞状细胞癌组织中p27kip1的表达水平,及其与年龄、肿瘤大小、淋巴结转移、分期、病理分级及生存率的相关性。结果p27kip1在肺鳞癌组织中高表达率为42%(20/48)。p27kip1的表达与肺鳞状细胞癌的分化程度呈正相关,P<0.01;而与患者的年龄、肿瘤大小、淋巴结转移及肿瘤分期无关。结论p27kip1的表达与肺鳞癌的病理分化程度呈显著正相关,对判断预后和指导治疗具有一定的意义。     

COX-2和EGFR在肺腺癌组织中的表达及其临床意义

目的探讨环氧合酶-2（COX-2）和表皮生长因子受体（EGFR）在人肺腺癌（pulmonary adenocarcinoma,PAC）组织中的表达及其临床意义。方法应用免疫组织化学二步法（非生物素）检测56例PAC、15例癌旁增生肺组织和10例正常肺组织中COX-2和EGFR蛋白的表达。结果COX-2、EGFR蛋白在PAC中的阳性率分别为75．00％、51．79％。在PAC中COX-2、EGFR蛋白的阳性率分别与癌旁增生肺组织、正常肺组织相比,差异均有统计学意义（P〈0．01）。COX-2蛋白表达与患者吸烟、肺腺癌的组织学分级、TNM分期以及淋巴结转移均密切相关（P〈0．05）：而EGFR蛋白表达仅与PAC患者的组织学分级、TNM分期、淋巴结转移密切相关（P〈0．05）。在56例人肺腺癌巾,COX-2、EGFR蛋白表达之间呈显著正相关（P=0．001,r=0．433）。结论COX-2和EGFR在人PAC巾呈高表达,二者可能协同促进PAC的发生发展以及侵袭和转移。     

Napsin A在肺腺癌中的表达及临床意义

目的探讨Napsin A对肺腺癌的诊断价值及与肺腺癌分化程度、临床病期和淋巴结转移的关系。方法采用SP免疫组织化学方法检测47例肺腺癌患者的肺癌组织中Napsin A的表达,并与癌旁正常肺组织、46例其他组织学类型的肺癌组织和19例良性肿瘤组织对比。结果肺腺癌组Napsin A表达阳性率87．2％,显著高于非肺腺癌组4．3％(X2=64．249,P<0．01)和良性肿瘤组21．1％(X2=27．317,P<0．01),但低于正常肺组织组100％(P<0．05);高分化、中分化和低分化肺腺癌组织中Napsin A表达阳性率分别为100％(20／20)、86．7％(13／15)和66．7％ (8／12),三者的阳性率具有显著性差异(X2=7．489,P<0．05);Ⅰ～Ⅱ期腺癌组Napsin A表达阳性率为100％(24／24),明显高于Ⅲ-Ⅳ期腺癌组73．9％(17／23),P<0．01;有淋巴结转移的肺腺癌组织Napsin A表达阳性率为72．7％(16／22),明显低于无淋巴结转移者100％(25／25),P< 0．05。结论Napsin A可以作为诊断肺腺癌的特异性肿瘤标记物,是判断肺腺癌恶性程度、临床病期及有无淋巴结转移的重要指标。     

子宫颈微偏腺癌的蛋白表达

目的 探讨对诊断子宫颈微偏腺癌(MDA)有价值的指标.方法 应用免疫组织化学EnYisionTM二步法检测9例MDA中CEA、Ki-67、p16、MUC6、MUCSAC、ER、PR、α-SMA的表达情况.另选12例正常子宫颈腺组织及21例其他类型腺癌组织作对照.结果 MDA中CEA、MUC6、α-SMA的阳性表达(表达率分别为66.67%、77.78%、88.89%)显著高于正常子宫颈腺体(0、8.33%、0),MDA中平均Ki-67标记指数(21.03±5.46)亦显著高于对照组(0.12±0.08),而ER、PR的阳性表达前者低于后者,差异均具有统计学意义(P＜0.05);p16、MUC5AC的阳性表达在对照组与MDA组之间差异无统计学意义(P＞0.1).MDA中MUC6蛋白的阳性表达率(77.78%)高于其他类型腺癌(14.29%),而p16蛋白的阳性表达率(11.11%)低于其他类型腺癌(71.43%),二者差异均具有统计学意义(P＜0.01);CEA、Ki-67、MUC5AC、ER、PR、α-SMA蛋白的阳性表达在两组之间差异无统计学意义(P＞0.05).结论 CEA、Ki-67、MUC6、α-SMA蛋白的阳性表达可能有助于MDA的诊断,腺上皮细胞ER、PR的阴性表达亦支持MDA.p16蛋白的过表达可能参与了部分普通型子宫颈腺癌的发生、发展,但在MDA中可能不起重要作用.     

CDHR2在肺腺癌中的表达及其与预后的关系

目的探讨CDHR2在肺腺癌(LUAD)组织中的表达及其与临床病理特征和预后的关系,并分析CDHR2与LUAD肿瘤免疫浸润的关系。方法挖掘TCGA、GEPIA数据库中CDHR2在LUAD中的表达及与预后的关系;免疫组织化学染色检测83例LUAD患者的癌组织及癌旁正常组织中CDHR2的表达情况,并分析其与患者临床病理特征及无病生存期(DFS)的关系。通过TIMER和CIBERSORT数据库分析CDHR2与LUAD肿瘤免疫浸润水平之间的关系。结果 TCGA数据集中515例LUAD组织的CDHR2表达水平显著高于59例癌旁正常组织(P<0.05)。GEPIA数据库发现CDHR2高表达与较差的总生存期(OS)有关(P<0.05)。免疫组化显示CDHR2蛋白在LUAD组织中的高表达率为66.3%(55/83),高于癌旁组织的37.3%(31/83),差异有统计学意义(P<0.05)。CDHR2蛋白表达与TNM分期有关(P<0.05)。CDHR2蛋白高表达患者的中位DFS为44.6(95%CI:39.5～49.7)个月,短于低表达患者的57.3(95%CI:49.9～64.8...     

Expression of nucleolar protein p120 predicts poor prognosis in patients with stage I lung adenocarcinoma

Background:P120 is a proliferation-associated nucleolar proteinfound in most human malignant tumors, but not in resting normal cells. In ourprevious studies, the expression of p120 was statistically correlated with theproliferation capacity in human lung cancer cells and could be a prognosticmarker for resected lung adenocarcinoma. Patients and methods:The expression levels of p120 in tumors wereassessed by immunohistochemistry in 59 patients with stage I lungadenocarcinoma who underwent radical resection. Using clinical follow-up data,the prognostic significance of p120 calculated by labeling indices wasevaluated using Coxs proportional hazard model. Results:A mean ± SD of the labeling index of p120 was35.3 ± 14.4%. No significant correlation was found betweenthe expression levels of p120 and clinicopathological factors. Using acutoff value of 35% in the labeling index of p120, patients with highexpression of p120 experienced early recurrence and shorter survival comparedwith those having low expression of p120 (P= 0.04). Multivariateanalysis revealed that p120 served as an independent and strongest prognosticfactor for resected lung adenocarcinoma (P= 0.033). Conclusion:This article provides the first evidence that theexpression levels of p120 in tumor tissues can be used as an independent andpowerful prognostic marker for resected stage I lung adenocarcinoma.     

肺腺癌患者EGFR和KRAS基因突变与预后的相关性研究

目的 探讨肺腺癌患者表皮生长因子受体(EGFR)和KRAS基因突变与预后的相关性.方法 选取134例肺腺癌患者的肺腺癌组织标本,应用探针扩增阻滞突变系统在PCR仪上进行EGFR和KRAS基因突变检测,分析EGFR和KRAS基因突变与肺腺癌患者临床病理特征及预后的关系.结果 134例患者中,EGFR基因突变53例,突变率为39.55%,KRAS基因突变6例,突变率为4.48%.肺腺癌患者EGFR基因突变率与年龄、吸烟史有关(P﹤0.01).EGFR基因突变型患者的KRAS基因突变率低于EGFR基因野生型患者(P﹤0.05).EGFR基因突变型患者的无进展生存期(PFS)长于EGFR基因野生型患者(P﹤0.05),KRAS基因野生型患者的PFS长于KRAS基因突变型患者(P﹤0.05).结论 EGFR基因突变的肺腺癌患者KRAS基因更倾向于野生型,EGFR基因突变型或KRAS基因野生型的肺腺癌患者PFS更长.     

Expression of axl in lung adenocarcinoma and correlation with tumor progression

We used the Transwell system to select highly invasive cell lines from minimally invasive parent cells, and we compared gene expression in paired cell lines with high and low invasive potentials. Axl was relatively overexpressed in the highly invasive cell lines when compared with their minimally invasive counterparts. However, there is only limited information about the role of Axl in cancer invasion. The biologic function of Axl in tumor invasion was investigated by overexpression of full-length Axl in minimally invasive cells and by siRNA knockdown of Axl expression in highly invasive cells. Overexpression of Axl in minimally invasive cells increased their invasiveness. siRNA reduced cell invasiveness as Axl was downregulated in highly invasive cells. We further investigated the protein expression of Axl by immunohistochemistry and its correlation with clinicopathologic features. Data from a study of 58 patient specimens showed that Axl immunoreactivity was statistically significant with respect to lymph node status (P < .0001) and the patient's clinical stage (P < .0001). Our results demonstrate that Axl protein kinase seems to play an important role in the invasion and progression of lung cancer.     

RACK1 regulates Src-mediated Sam68 and p190RhoGAP signaling

RACK1 is the founding member of a family of receptors for activated C kinase collectively called RACKs. Upon activation of PKC, RACK1 co-localizes with the Src tyrosine kinase at the plasma membrane and functions as a substrate, binding partner and inhibitor of Src (as measured in vitro), and a growth inhibitor in NIH 3T3 cells. To further analyze the function of RACK1 in Src and PKC signaling, we utilized cell-permeable peptides that modulate the interaction of RACK1 and betaIIPKC, thereby affecting betaIIPKC translocation and function. We found that the association of betaIIPKC and RACK1 is necessary for Src phosphorylation of RACK1. Src activity is required for tyrosine phosphorylation of RACK1, and for RACK1 binding to Src, but not to betaIIPKC. Endogenous Src kinase activity, as measured by phosphorylation of Sam68 (a mitotic-specific Src substrate involved in cell cycle regulation and RNA splicing) or p190RhoGAP (a Src substrate and GTPase-activating protein involved in actin reorganization), increases with disruption of the Src-RACK1 complex, and decreases with enhanced complex formation. RACK1 inhibits Src-mediated p190RhoGAP signaling and actin cytoskeleton rearrangement. Thus, RACK1 functions as an endogenous inhibitor of the Src kinase in diverse signaling pathways that regulate distinct cellular functions. Our results demonstrate the potential for using peptide modulators of Src activity as a tool for uncovering the function of Src in cells.     

Expression of UbcH10 in pancreatic ductal adenocarcinoma and its correlation with prognosis

The aim of this current study was to investigate the clinicopathologic features and prognostic significance of UbcH10 in pancreatic ductal adenocarcinoma (PDA). Real-time quantitative RT-PCR was employed to examine UbcH10 expression in 20 pairs of PDA and adjacent non-cancerous tissues. In addition, UbcH10 expression was analyzed by immunohistochemistry in 94 clinicopathologically characterized PDA cases. The correlation of UbcH10 expression with patients’ survival rate was assessed by Kaplan–Meier and Cox regression. Our results showed that the expression levels of UbcH10 mRNA and protein in PDA tissues were both significantly higher than those in non-cancerous tissues. Simultaneously, high expression of UbcH10 was significantly correlated with the clinical stage (p?<?0.001), degree of histological differentiation (p?<?0.001), and lymph node metastasis (p?=?0.001). Moreover, high expression of UbcH10 was significantly associated with poor overall survival in PDA patients. In conclusion, UbcH10 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for PDA.     

Oct-4蛋白在直肠癌中的表达及其与患者预后的相关性

目的 观察直肠腺癌组织中胚胎干细胞标志物Oct-4蛋白的表达,并对其与直肠癌患者预后的关系进行探讨.方法 应用免疫组织化学ABC法检测52例直肠癌组织中Oct-4蛋白的表达,分析Oct-4蛋白表达与预后、分期、分化程度的关系.结果 Oct-4蛋白表达主要位于直肠癌细胞胞质内,其阳性细胞数为0％ ～ 18.5％,表达阴性和阳性者分别有38例(73.1％)和14例(26.9％).Oct-4表达阳性率与性别、年龄、临床分期和病理学分级之间无相关性(P＞0.05).Oct-4表达阴性和阳性者的3年局部无复发率分别为83.5％和75.0％,两者间差异无统计学意义(P =0.583);3年无远处转移率分别为88.6％和61.9％,两者间差异有统计学意义(P =0.035);3年生存率分别为77.9％和50.0％,差异有统计学意义(P =0.037).结论 Oct-4在直肠腺癌组织中有不同程度的表达,Oct-4阳性表达与远处转移率及总生存率相关,与3年局部无复发率无关.     

Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma

p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non-small-cell lung cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same cohort. The expression of NRF2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma (n = 72), squamous cell carcinoma (n = 31), and large cell carcinoma (n = 6). Accumulation of NRF2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF2 did not correlate with each other, but both were associated with worse lung cancer-specific survival (P = 0.0003 for NRF2; P = 0.0130 for p62). NRF2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma (P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF2 and p62 were both independent factors predicting worse lung cancer-specific survival (P < 0.0001 for NRF2 and P = 0.04 for p62). This study revealed that both NRF2 and p62 are independent prognostic factors for NSCLC. The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma.