Nucleostemin基因在非小细胞肺癌组织中的表达及意义

目的探讨Nucleostemin(NS,核干细胞因子)基因在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及临床意义。方法利用RT-PCR法检测13对NSCLC组织和癌旁正常组织中NS mRNA的表达;采用免疫组织化学SP法检测73例NSCLC组织和13例癌旁正常组织中NS蛋白的表达,并分析与NSCLC患者临床病理特征的关系。结果 NSCLC组织中NS mRNA相对表达强度(0.848±0.305)显著高于癌旁正常组织(0.153±0.020)(t=8.712,P0.01)。NS蛋白在NSCLC中的表达率为58.9%(43/73)显著高于癌旁正常组织中的表达率0%(0/13)(χ2=15.315,P0.01)。NS蛋白的表达率与NSCLC的组织类型及分化程度相关,腺癌组织的表达率为76.5%(26/34)明显高于鳞癌组织的表达率43.6%(17/39)(χ2=8.113,P0.01);低分化组织的表达率81.5%(22/27)明显高于高、中分化组织的表达率45.7%(21/46)(χ2=9.023,P0.01),而与患者性别、年龄、肿瘤大小、TNM分期及淋巴结转移无关(P0.05)。结论 NS基因mRNA及蛋白在NSCLC组织中高表达,对肿瘤细胞的恶性增殖起了重要作用,是一个新的有应用价值的肿瘤分子标志物。     

SRPX2在非小细胞肺癌中的表达及其临床意义

目的探讨含Sushi重复蛋白X连锁2(Sushi repeat containing protein,X-linked 2,SRPX2)在非小细胞肺癌(nonsmall cell lung cancer,NSCLC)组织中的表达及其临床意义。方法采用免疫组织化学方检测93例NSCLC组织和23例癌旁正常组织中SRPX2的表达,并分析与NSCLC患者临床病理特征及预后的关系。结果 SRPX2在NSCLC中的表达率为52.7%(49/93),显著高于癌旁正常组织中的表达率0%(0/26),在Ⅲ期中的阳性表达率明显高于Ⅰ、Ⅱ期,有淋巴结转移组织中的阳性表达率明显高于无淋巴结转移组织,而与患者性别、年龄、有无吸烟、组织学类型及分化程度无关。Kaplan-meier生存曲线显示,SRPX2阳性表达的患者生存率明显低于表达阴性者。结论 SRPX2在NSCLC组织中阳性表达,对肿瘤细胞的浸润和转移起促进作用,阳性表达患者生存率低。     

P-gp、TopoⅡ在非小细胞肺癌中的表达

为明确化疗前非小细胞肺癌（nonsmall cell lung cancer,NSCLCL)中P－糖蛋白（P－Glycoprotein,P-gp)、拓扑异构酶Ⅱ（TopoisomeraseⅡ,TopoⅡ）的不同表达与NSCLC的组织类型、细胞分化程度、TNM分期是否相关,是否存在原发耐药,是否影响NSCLC患的预后,本实验采用S－P免疫组化方法,检测97例化疗前NSCLC患中P-gp、TopoⅡ的表达情况。结果表明：P－gp在腺癌中高表达,在有淋巴结转移的病例中高表达,且P-gp和TopoⅡ在表达上虽不具有相关性,但两表达程度及其交互作用都是NSCLC患预后的影响因素。     

非小细胞肺癌WWOX和ALDH1水平与血管生成的相关性分析

目的检测WWOX、ALDH1和CD34蛋白在非小细胞肺癌(non-small cell lung carcinoma,NSCLC)中的表达,并分析它们之间的相互关系以及与NSCLC患者各临床参数之间的关系。方法采用免疫组织化学法检测120例NSCLC和60例正常肺组织中WWOX、ALDH1和CD34蛋白的表达,并计数MVD(通过CD34标记阳性的管腔结构来计数)情况。结果WWOX在NSCLC中阳性表达率低,阳性率与NSCLC分化程度、淋巴结转移及临床分期之间呈负相关;ALDH1在NSCLC中阳性表达率高,阳性率与NSCLC分化程度、淋巴结转移及临床分期之间呈正相关。MVD计数在分化程度差、TNM分期高及淋巴结转移的NSCLC中较高。Spearman相关分析发现,WWOX的阳性率和ALDH1的阳性率及MVD计数之间呈负相关;ALDH1的阳性率与MVD计数之间呈正相关。结论 WWOX和ALDH1的表达可能参与了NSCLC的发生、发展、侵袭和转移过程,并促进NSCLC中的血管生成;在NSCLC中检测WWOX和ALDH1的表达和MVD计数情况可以早期预测其浸润和转移。     

整合素连接激酶和基质金属蛋白酶-9在非小细胞肺癌表达的研究

目的探讨整合素连接激酶(integrin-linked kinase,ILK)和基质金属蛋白酶(matrix metalloproteinase-9,MMP-9)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的关系.方法应用SP免疫组织化学方法检测74例手术切除NSCLC标本和10例正常肺组织中ILK和MMP-9蛋白的表达.结果在NSCLC组织中ILK和MMP-9蛋白的阳性表达率分别为74.5%(55/74)和71.6%(53/74),均明显高于正常肺组织(P<0.05).ILK 阳性表达率与原发灶大小,组织学类型,分化程度,淋巴结转移,临床分期均无密切关系(P>0.05);MMP-9阳性表达率与原发灶大小,组织学类型,分化程度,淋巴结转移,临床分期均有密切关系(P<0.05).结论 ILK和MMP-9蛋白过度表达可能分别在NSCLC的发生和发展过程中起重要作用.     

survivin在非小细胞肺癌中的表达及其与bc1-2、p63表达的关系

目的:探讨survivin在非小细胞肺癌组织(non small cell lung cancer,NSCLC)中的表达,及其与bc 1 2、p63蛋白表达的相关性。方法:应用二步法免疫组织化法,检测survivin、bc 1-2、p63蛋白在60例NSCLC组织和20例正常肺组织中的表达。结果:肺癌组织中的survivin蛋白阳性率(56．67%)明显高于正常肺组织15%),有显著性差异;(p＜0．05)Ⅲ期surviving蛋白阳性表达率72．73%(16/22)明显高于Ⅰ Ⅱ期survivin47．37%(18/38)。有显著差异;(p＜0．05)survivin蛋白表达与患者年龄、病理类型、组织分化程度,淋巴结转移情况无关(P＞0．05)NSCLC组织bc 1-2蛋白表达阳性、阴性组中,survivin蛋白阳性表达率分别为66．67% (18/27)和48．48%(16/33),两者比较,差异有显著性(P＜0．05);p63蛋白表达阳性、阴性组中,survivin蛋白阳性表达率分别为53．33%(16/30)和60%(18/30),两者比较,差异有显著性(P＜0．05)survivin,蛋白与bc 1-2蛋白的表达呈正相关。survivin蛋白与p63蛋白的表达呈正相关。结论:survivin在NSCLC组织中表达上调,通过抑制细胞凋亡,在NSCLC的发生和发展中起到重要作用。survivin,bc 1-2与p63它们分别在肺癌发生发展过程中不同途径上抑制肺癌细胞的凋亡,对肺癌早期诊断有一定的意义。对3种蛋白进行联合检测,更有利于肺癌的早期诊断和判断肺癌的分化程度、临床分期、淋巴结是否转移及病人的预后。survivin与bc1-2及survivin与p63可能起协同作用,并可能会成为NSCLC基因治疗的新靶点。     

miR-191在非小细胞肺癌中的表达及其临床意义

目的:探讨miR-191在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其临床意义。方法:采用实时荧光相对定量聚合酶链式反应(quantitative realtime polymerase chain reaction,qRT-PCR)技术检测非小细胞肺癌患者的癌组织及癌旁组织中miR-191的表达水平,并分析其与患者临床病理特征及生存期的相关性。结果:与癌旁组织比较,癌组织中miR-191的表达显著上调。组织分化程度低或有淋巴结转移的NSCLC患者癌组织中miR-191表达明显高于组织分化程度高或无淋巴结转移的NSCLC患者(P0.05),癌组织高表达miR-191的NSCLC患者生存期明显短于癌组织低表达miR-191的NSCLC患者(P0.05)。结论:miR-191在非小细胞肺癌中表达上调,与组织分化程度、淋巴结转移和患者生存期有关。     

C/EBPα在非小细胞肺癌中的表达及其与微血管密度的关系

目的:探讨C/EBPα在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其与肿瘤微血管密度(microvessel density,MVD)的关系.方法:应用免疫组织化学EnVision法检测40例手术切除的NSCLC组织及其配对的40例距肿瘤＞5 cm以上癌旁正常肺组织中C/EBPα蛋白的表达,并分析C/EBPα在NSCLC中的表达与其临床病理特征的关系.采用CD34标记肺癌组织中的肿瘤微血管,分析C/EBPα的表达与肿瘤MVD的关系.结果:NSCLC组织中C/EBPα的阳性表达率明显低于癌旁正常肺组织(P＜0.05).C/EBPα与NSCLC患者的年龄、性别、TNM分期及有无淋巴结转移均无关(P＞0.05),与NSCLC组织的分化程度及病理类型有关(P＜0.05).在NSCLC组织中,C/EBPα蛋白表达阳性组MVD明显低于C/EBPα蛋白表达阴性组(P＜0.05).结论:C/EBPα在NSCLC中的低表达可能通过调节MVD介导NSCLC的发生和发展.     

ERCC-1和RRM-1在NSCLC中的表达及其病理临床意义

目的检测核苷酸切除修复(NER)系统的ERCC-1和RRM-1在非小细胞肺癌(NSCLC)组织中的表达并分析其表达的病理临床意义,为探索NSCLC的有关发生机制及术后辅助化疗提供有用的实验依据。方法应用免疫组织化学二步法检测128例NSCLC组织中ERCC-1和RRM-1的表达,以10例支气管扩张症肺组织作为对照。结果1.ERCC-1在NSCLC组织中的总体阳性表达率为44.53%(57/128),在对照组肺组织气道上皮的阳性表达率为100%(10/10),ERCC-1在NSCLC组织和对照组的阳性率差异有统计学意义(P<0.05);RRM-1在NSCLC组织中的总体阳性表达率为75%(96/128),在对照组肺组织气道上皮不表达,RRM-1在NSCLC组织和对照组的阳性率差异有统计学意义(P<0.05)。2.ERCC-1的表达与NSCLC患者的年龄、组织学类型及分化程度存在相关性(P<0.05);RRM-1的表达与NSCLC患者的年龄存在相关性(P<0.05)。NSCLC组织中ERCC-1与RRM-1的表达呈正相关(P<0.01)。结论ERCC-1表达降低或缺失可能与NSCLC发生有关;NSCLC组织中存在...     

转录因子Snail在非小细胞肺癌中的表达及意义

目的检测转录因子Snail mRNA及蛋白在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达,探讨Snail在NSCLC发生发展中的作用。方法采用免疫组织化学、RT-PCR的方法检测NSCLC、癌旁相对正常肺组织(>5cm)中转录因子Snail蛋白及mRNA的表达,并分析其与临床病理参数之间的关系。结果 NSCLC组织中Snail mRNA的阳性表达率(82.7%)高于癌旁相对正常肺组织(23.1%,P<0.05);NSCLC组织中Snail mRNA的阳性表达量(1.368±0.614)高于癌旁相对正常肺组织(0.579±0.217,P<0.05)。NSCLC组织中Snail蛋白的阳性表达率(80.8%)高于癌旁相对正常肺组织(23.1%,P<0.05),且癌组织中Snail蛋白阳性表达率与TNM分期、淋巴结转移有关(P<0.05),而与组织分型、分化程度、吸烟史无关(P>0.05)。结论 NSCLC的癌变、侵袭、转移可能与Snail蛋白、mRNA的高表达有关。     

Immunolocalization and cell expression of lung resistance-related protein (LRP) in normal and tumoral human respiratory cells.

Lung resistance-related protein (LRP) is an integral part of the multidrug resistance (MDR) phenotype involved in cell resistance toward xenobiotics or chemotherapy. The aim of this study was to compare the intracellular localization and cell expression of LRP in normal bronchial cells and their tumoral counterparts from non-small cell lung cancer (NSCLC). LRP expression was also investigated concurrently with DNA ploidy and chromosome 16 (lrp gene locus) aberrations. Confocal microscopy showed that LRP localization was exclusively intracytoplasmic regardless of the cell type and was never observed in the nuclear pore complex. Flow cytometry demonstrated a similar level of LRP expression in normal bronchial cells and in cancer cells from NSCLC samples. FISH analysis, performed to evaluate the number of chromosome 16 and lrp loci, demonstrated a significant gain of chromosome 16 in DNA aneuploid tumors. Furthermore, we did not find any link between LRP expression and DNA ploidy status or chromosome 16 number. These results suggest that LRP expression observed in NSCLC, maintained through the carcinogenesis process of respiratory cells, is not altered by the increased number of copies of chromosome 16 and probably controlled by mechanisms different from those of MRP1 expression, whereas both proteins are associated with the MDR phenotype.     

整合素连接激酶在非小细胞肺癌中的表达及意义

目的了解整合素连接激酶(intergrin-linked kinase ILK)在非小细胞肺癌中的表达情况．与临床病理特征之间的关系及与非小细胞肺癌患预后的关系并探讨其意义。方法采用免疫组织化学SP法和免疫蛋白印迹法检测ILK在101例非小细胞肺癌(60例鳞癌,41例腺癌)中的表达。结果(1)ILK在非小细胞肺癌组织中的表达高于正常组织且在鳞癌组织中ILK的表达随着分化程度的降低而提高;(2)ILK的表达与临床分期,淋巴结转移等临床病理特征之间无联系(3)ILK的不同表达与非小细胞肺癌患的预后无关。结论目前国内外尚未有ILK在肺癌中的研究,我们的研究表明ILK在非小细胞肺癌中的表达与非小细胞肺癌组织的组织类型来源和恶性程度有关,并可能参与了非小细胞肺癌的发生发展过程。     

Expression of multidrug resistance-related protein (MRP-1), lung resistance-related protein (LRP) and topoisomerase-II (TOPO-II) in Wilms' tumor: immunohistochemical study using TMA methodology

Aims: MRP-1, LRP and TOPO-II are all associated with protection of the cells from the adverse effects of various chemotherapeutics. The aim of this study was to measure the expression of these proteins in Wilms' tumor (WT). Materials and Methods: TMA block was constructed from 14 samples of WT's and from xenografts derived from them. Sections of the TMA were used for immunostaining against MRP-1, LRP and TOPO-IIa. Results: All normal kidneys expressed MRP-1 but were either weakly or negatively stained for LRP and TOPO-IIa. In WT samples, MRP-1 was universally expressed, exclusively in the tubular component, while there was no expression of LRP and TOPO-IIa showed heterogeneous distribution. The xenografts varied in their MRP-1 and TOPO-IIa expression and exhibited weak/negative staining of LRP. Conclusions: This study shows that although all the proteins evaluated, had different expression patterns in the tumor samples, the most prominent changes in expression were found for MRP-1. The exact clinical implications of these changes in expression and their relevance to the resistance of these tumors to chemotherapy requires further investigation. The finding of different expression profiles for the multidrug resistance proteins in the original WT's and their xenografts suggests that the results of animal cancer models may be difficult to interpret.     

凋亡抑制蛋白Livin和抑癌基因p53在非小细胞肺癌中的表达及临床病理学意义

目的检测livin和P53蛋白在非小细胞肺癌(NSCLC)组织中的表达并分析其临床病理学意义。方法采用免疫组织化学(SABC)的方法检测livin和P53蛋白在40例NSCLC患者肺癌组织切片中的表达,分析其与临床病理学参数之间的关系。结果40例NSCLC中livin和P53蛋白阳性表达率分别为47.5%和52.5%,在淋巴结转移的NSCLC组织中livin的阳性率明显高于无淋巴结转移的肺癌组织(P<0.05),且与肺癌不同分期有关(P<0.05)。P53蛋白表达亦与肿瘤分期有关,P53在鳞癌中的表达率显著高于腺癌(P<0.05)。P53和livin均与年龄、性别、肿瘤分化程度等临床病理学参数无关(P>0.05)。Livin与P53蛋白的表达无明显相关性(P>0.05)。结论livin与P53异常表达与NSCLC的恶性生物学行为有关,其表达对临床上判断NSCLC的预后有重要意义。     

非小细胞肺癌组织中VEGF与P53蛋白表达及意义

目的:探讨VEGF和P53在非小细胞肺癌(NSCLC)中的表达及其生物学行为的关系。方法:采用免疫组织化学方法,对病理确诊的62例非小细胞肺癌组织进行VEGF和P53表达的检测。结果:62例非小细胞肺癌VEGF阳性表达率58.1%(36/62),其表达与NSCLC的组织分化程度、生存期有相关性(P<0.05),与组织学类型、有无淋巴结转移、临床病理分期无关。P53阳性表达率46.8%(29,62),表达与肿瘤组织类型、TNM分期、有无淋巴结转移无关(P<0.05)。结论:VEGF和P53可作为评价非小细胞肺癌预后的重要指标。用免疫组化检测出P53蛋白可间接反映P53基因的突变。本组资料检测的结果显示,P53基因阳性表达率46.8% (29/62),表明近一半肺癌病例已失去P53蛋白的抑癌功能,且P53基因的突变可能与非小细胞肺癌的发生有关。P53和VEGF都是潜在的新型肿瘤表型标志物,它们的检测可作为肿瘤病理分级诊断的主要参考依据。同时检测P53和VEGF的表达状态,可通过肿瘤血管形成的生物学行为信息,进一步研究肿瘤血管形成的分子水平调控机制,这有助于抗肿瘤药物的开发研究。     

HPV感染、FHIT蛋白表达与非小细胞肺癌的相关性研究

目的探讨人乳头瘤病毒感染在NSCLC发生中的病因学意义,同时分析FHIT蛋白表达与NSCLC发生及HPV感染的关系.方法采用PCR方法选用通用型引物和HPV16、18型特异性引物分别对42例NSCLC及14例肺良性病变组织进行检测.免疫组化SP法检测FHIT蛋白的表达水平.结果 HPV DNA检出率肺癌组为42.9%,肺良性病变组为7.1%,二者有显著性差异(P<0.05).HPV感染率在肺鳞癌(53.6%)显著高于腺癌(21.4%),且随着分化程度降低,其感染率增高,在吸烟患者(57.7%)显著高于不吸烟患者(18.8%);FHIT蛋白异常表达率肺癌组为61.9%,与肺良性病变组(28.6%)比较有显著性差异(P<0.05).肺癌中HPV阳性组FHIT蛋白异常表达率为83.3%,明显高于HPV阴性组(45.8%,P<0.05).结论 HPV感染与NSCLC组织学类型、分化程度及吸烟有关,它可能是导致NSCLC发生的重要病因学因素之一;FHIT蛋白异常表达与NSCLC发生及HPV感染有关,HPV可能通过诱导FHIT表达异常参与NSCLC的发生发展过程.     

Detection of the Mr 110,000 lung resistance-related protein LRP/MVP with monoclonal antibodies.

The Mr 110,000 lung resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.     

Lung resistance protein analysis in testicular cancer

Germ cell testicular cancers are well-curable neoplasms, because total remission can be achieved in about 80% of the cases. However, 15-20% of the patients die due to drug resistance (DR). A number of mechanisms of the multidrug resistance phenotype are known, including MDR/P-glycoprotein (P-gp) and the so-called multidrug resistance associated protein (MRP). Lung Resistance Protein (LRP) is an ATP dependent membrane transporter protein associated with MDR. In our present work we studied the expression of LRP in testicular cancers. LRP expression was determined by immunohistochemistry (IH), Western blot (WB) and RT-PCR techniques. Clinical resistance was defined in accordance with the clinical oncologic rules. In 29 (41%) of 70 primary testicular tumours and in 22 (63%) of 35 cases, elevated LRP levels were established by IH and WB, respectively. In the latter 63%, the LRP mRNA levels were elevated as well. Six cases of the 15 seminomas and 23 cases of the nonseminomatous germ cell tumours (NSGCT) proved to be positive. No relationship was demonstrated between LRP expression and the stage of the disease. Despite the LRP positivity of 6 tumour samples, all of the seminomas proved sensitive. Of the 39 sensitive NSGCT, 27 cases were LRP-negative, whereas 11 tumour samples of 16 patients belonging to the resistant group proved LRP-positive (p=0.04). The authors concluded that the expression of LRP is responsible for clinical drug resistance in non-seminomatous testicular cancer patients.     

Potential predictive value of comutant LRP1B and FAT for immune response in non-small cell lung cancer: LRP1B and FAT comutation enhance immune response

BackgroundPreliminary investigation revealed that Low-density lipoprotein receptor-related protein 1b (LRP1B) and FAT atypical cadherin (FAT) family mutation might serve as immune regulators under certain tumor microenvironment.Experimental designWe curated a total of 70 non-small cell lung cancer (NSCLC) patients who harbored alterations in LRP1B and/or FAT family (FAT1/2/3/4) based on next-generation sequencing (NGS) to analyze multiple-dimensional data types, including comutant status, tumor mutation burden (TMB), programmed death receptor ligand 1 (PD-L1) expression, T cell-inflamed gene expression profiling (GEP) and therapy response.Results20 patients with co-occurring mutations in LRP1B and FAT1/2/3/4 revealed a relatively higher TMB level of 17.05 mut/Mb compared with 7.60 mut/Mb and 8.80 mut/Mb in single LRP1B and FAT mutation groups, respectively. LRP1B and FAT members showed specifically enriched T cell-inflamed genes and the co-occurring mutant TP53 status in NSCLC patients who harbor LRP1B/FAT comutations.ConclusionsThis work provides evidence that co-occurring mutations of LRP1B and FAT in NSCLC may serve as a group of potential predictive factors in guiding immunotherapy on the basis of their association with TMB status.