ILK在肺鳞状细胞癌和肺腺癌的表达及其与临床病理特征和预后的关系

目的 探讨ILK在肺鳞状细胞癌和肺腺癌组织中的表达情况,及其与病理分型、肿瘤分化、分期、淋巴结转移及预后的关系。方法采用S-P免疫组织化学方法和Western Blot法,检测肺鳞状细胞癌和肺腺癌组织及相应癌旁肺组织中整合连接激酶（integrin-linkedkinase,ILK）的表达情况,并结合临床和病理资料进行分析。结果免疫组化结果显示：ILK在53／76（70％）的肺癌组织中阳性表达。其中鳞状细胞癌阳性率75％（33／44）,腺癌阳性率62．5％（20／32）,其表达与肺鳞状细胞癌的分化呈负相关（P〈0．01）,与临床分期（P〈0．01）、淋巴结转移（P〈0．01）呈正相关;与肺腺癌的临床分期（P〈0．01）和淋巴结转移（P〈0．01）正相关,与分化程度无相关性（P〉0．05）。同时,其表达与患者的生存时间呈负相关（P〈0．01）,与年龄、性别、肿瘤大小和组织类型等因素无关。Western Blot法进一步证实ILK在肺癌组织中的表达显著高于癌旁正常肺组织（P〈0．01）,其表达与肺癌的分化（P〈0．01）显著负相关。结论肺鳞状细胞癌和肺腺癌中,ILK与肺癌的侵袭和转移有关。ILK可作为判断肺鳞状细胞癌和肺腺癌预后的参考指标。     

转录因子Hey1在非小细胞肺癌中的表达及临床意义

目的检测Hey1与Notch1在非小细胞肺癌组织中的表达,探讨Hey1在非小细胞肺癌中的表达与Notch1的表达、各临床病理特征之间的关系。方法制作组织芯片,采用免疫组织化学染色检测Notch1和Hey1在246例非小细胞肺癌组织及相应117例癌旁正常肺组织中的表达,应用SPSS 21.0进行统计分析。结果 Notch1在肺鳞癌、肺腺癌和癌旁正常肺组织的阳性率分别为78.8%,28.9%和30.8%,Hey1在肺鳞癌、肺腺癌和癌旁正常肺组织中的阳性率分别为79.7%,23.4%和33.3%;肺鳞癌患者Notch1阳性表达与TNM分期和淋巴结转移情况呈正相关;肺鳞癌患者Hey1阳性表达与TNM分期呈正相关,与肿瘤分化程度呈负相关;Spearman相关分析显示,肺鳞癌和肺腺癌组织中Notch1表达与Hey1表达具有显著的正相关关系。结论 Hey1和Notch1与肺鳞癌的恶性程度密切相关,可能是肺鳞癌发生、发展的重要参与因子。     

MCM7与RACK1在肺癌中的表达及其临床意义

目的探讨MCM7与RACK1在各类型肺癌中的表达及其相关性。方法收集肺腺癌150例、鳞癌150例、大细胞癌20例和小细胞癌50例及其癌旁正常肺组织石蜡标本,采用免疫组织化学S-P法检测各类型肺癌组织和癌旁正常肺组织中MCM7与RACK1的表达,并分析二者与肺癌临床病理因素的关系。结果 MCM7与RACK1在癌组织中的表达明显高于癌旁正常肺组织;χ~2检验结果显示肺癌中MCM7与RACK1的表达均与肺癌的病理分级、淋巴结转移、组织学分类和临床TNM分期相关;Pearson相关性分析结果显示,肺癌中MCM7与RACK1的表达呈正相关;Kaplan-Meier法分析显示MCM7与RACK1高表达患者生存时间缩短。结论肺癌中MCM7与RACK1的表达呈正相关,二者表达在肺癌中起促进作用,可作为检测肺癌细胞的增殖状态、新的判断预后的重要因子,以其为靶向进行临床治疗的重要指标。     

阿尔茨海默病转基因模型Tg2576小鼠血清的代谢组学研究

目的 Tg2576转基因小鼠与阿尔茨海默病(Alzheimer’s disease,AD)患者的病理改变相近,本文动态研究了Tg2576小鼠在AD发病不同阶段的血清代谢物特征,为临床AD的早期诊断提供代谢依据。方法收集Tg2576小鼠在AD发病初期(6个月)和末期(12个月)时的血清样本,采集样本的1HNMR谱并运用多变量分析方法进行代谢特征的分析。结果结果显示Tg2576与C57小鼠分别在6和12个月时的血清代谢特征有明显差异,且不同AD发病阶段的Tg2576小鼠具有明显的代谢差异。与C57小鼠相比,在AD出现的初期阶段,Tg2576小鼠血清中乳酸、肌醇和氨基酸(如亮氨酸、异亮氨酸、丙氨酸)的含量升高,而脂质、胆碱、磷脂酰胆碱/甘油磷脂酰胆碱、甜菜碱、甘氨酸和葡萄糖含量降低;在AD发病的末期,血清中乳酸、肌醇和丙氨酸的含量继续上升,脂质、胆碱、磷脂酰胆碱/甘油磷脂酰胆碱、甜菜碱和甘氨酸含量持续降低,同时谷氨酸和肌酸含量初步显示出下降趋势。通过比较AD的初期和末期血清代谢物,我们能够发现疾病末期血清中乳酸、肌醇和丙氨酸含量升高,脂质、胆碱、磷脂酰胆碱、甘油磷脂酰胆碱含量降低。在这些代谢物中,乳酸、脂质、胆碱、磷脂酰胆碱和甘油磷脂酰胆碱在AD发生初期已具有显著性变化,且与AD发生的严重程度密切相关。结论结果表明Tg2576小鼠中乳酸与阿尔茨海默病程度的加重呈正相关变化,而脂质、胆碱、磷脂酰胆碱和甘油磷脂酰胆碱呈负相关改变,且这些代谢物随着疾病的发展呈动态进行性变化,可能是AD早期诊断的重要代谢标志物。     

基于WGCNA和SVM-RFE算法挖掘肺腺癌诊断和预后基因标志物

目的 肺癌是世界上最常见的癌症之一,在众多肺癌患者中,肺腺癌(lung adenocarcinoma,LUAD)的死亡率最高.基因表达谱的变化与肿瘤的发生和发展过程有关,通过识别与LUAD患者相关的诊断和预后基因标志物,可以为肺腺癌的预防和治疗提供理论依据.方法 本研究以肿瘤基因组图谱(The Cancer Gene ...     

肺癌患者血清CEA、CYFRA21-1和NSE的检测及临床意义

目的探讨外周血癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和神经元特异性烯醇化酶(NSE)的检测对肺癌的诊断、病理分型和疗效判断的临床用价值。方法采用化学发光法检测了62例肺癌患者、54例良性肺部疾病患者、36例健康人、40例肺癌患者手术前后血清CEA、CYFRA21-1和NSE的水平。结果肺癌患者手术前血清CEA、CYFRA21-1和NSE的含量明显高于良性肺部疾病组及正常对照组(P0.01)。鳞癌组、腺癌组和小细胞癌组之间肿瘤标志物CEA、CYFRA21-1和NSE水平差异有统计学意义。CEA阳性率以腺癌组最高(84%),CYFRA21-1阳性率以鳞癌组最高(85.2%),NSE阳性率以小细胞癌组最高(80.0%)。手术治疗后未复发转移组CEA、CYFRA21-1和NSE水平低于术前,而复发转移组与术前比变化不显著(P0.05)。结论血清CEA、CYFRA21-1和NSE的检测对不同病理类型肺癌患者的诊断、病情检测及疗效判断有较好的临床参考价值。     

非小细胞肺癌中肿瘤标志物CEA、SCC、NSE表达水平的临床分析

目的分析和探讨肿瘤标志物CEA、SCC、NSE在非小细胞肺癌临床预诊中的价值。方法对83例非小细胞肺癌患者和50例健康人进行肿瘤标志物CEA、SCC、NSE检测,从非小细胞肺癌不同分期、不同病理类型及综合阳性率等方面进行观察分析。结果非小细胞肺癌组CEA阳性率各期均在50%以上,NSE阳性率随肿瘤分期递增,平均为51.8%,二者的测定值Ⅲb、Ⅳ期均明显高于Ⅱ、Ⅲa期(P<0.01);SCC阳性率25%~33.3%,测定值各期差异不显著(P>0.05)。CEA以腺癌阳性率最高,测定值腺癌组明显高于其他组(P<0.01);SCC鳞癌组的阳性率和测定值均高于其他组(P<0.05);NSE鳞癌和大细胞未分化癌阳性率均在50%以上,测定值鳞癌、大细胞未分化癌和其他类型明显高于腺癌组(P<0.01)。不同病理类型综合阳性率的表达:有一项以上阳性者鳞癌为71.1%,腺癌为81.3%,大细胞未分化癌为80%,其他类型为100%。结论CEA、SCC、NSE三者联合检测综合阳性率明显提高。NSE敏感性高,特异性差,可作为肺癌早期诊断的辅助手段。     

早期肺癌诊断中PET/CT的应用价值

目的:探讨PET/CT在早期肺癌诊断中的应用价值.方法:应用PET/CT对16例肺部孤立性病灶进行PET/CT检查,手术切除病灶组织送病理检查,以判断诊断符合率与细胞类型.结果:16例肺病灶患者PET/CT检查与手术切除组织病理结果相比较,诊断符合率为87.5%,其中腺癌13例(包括细支气管肺泡细胞癌6例),鳞癌2例,肺粘膜相关B细胞淋巴瘤1例.结论:结合临床症状,PET/CT检查能够准确的对肺癌做出早期诊断,及早治疗,改善患者预后     

血清肿瘤标志物CEA、CA199及CA153联合检测对肺癌的诊断价值

目的：评价血清CEA、CA199及CA153联合检测对肺癌诊断及分期的临床价值。方法：用化学发光分析法测定144例不同类型及分期的肺癌患者、92例肺良性疾病患者及76例健康体检者血清CEA、CA199及CA153水平的变化。结果：肺癌组血清CEA、CA199及CA153水平均高于正常对照组及肺良性疾病患者,有显著性差异,且TNM分期越晚,其水平越高;3项肿瘤标志联合检测可提高敏感性及准确性。结论：CEA、CA199及CA153联合检测可以为肺癌的诊断及分期提供有价值的实验室依据。     

红桂木凝集素受体在肺癌组织的表达及意义

为探讨肺癌中红桂木凝集素(ALL)受体的表达及其临床意义,本研究应用凝集素亲和组化法检测45例原发性肺癌(鳞癌25例,腺癌20例),阴性对照采用20例癌旁正常肺组织。凝集素组化显示,28例(62.2%)肺癌和3例(15%)癌旁正常肺组织的红桂木凝集素受体表达阳性,差异具有显著性。红桂木凝集素受体表达与肺癌TNM分期、淋巴结转移、分化程度有关,但与年龄、性别、肿瘤大小、病理类型无关。     

Chromatin patterns associated with lung adenocarcinoma progression

The development and progression of lung adenocarcinoma, one of the most common cancers, is driven by the interplay of genetic and epigenetic changes and the role of chromatin structure in malignant transformation remains poorly understood. We used systematic nucleosome distribution and chromatin accessibility microarray mapping platforms to analyze the genome-wide chromatin structure from normal tissues and from primary lung adenocarcinoma of different grades and stages. We identified chromatin-based patterns across different patients with lung adenocarcinoma of different cancer grade and stage. Low-grade cancers had nucleosome distributions very different compared with the corresponding normal tissue but had nearly identical chromatin accessibility. Conversely, nucleosome distributions of high-grade cancers showed few differences. Substantial disruptions in chromosomal accessibility were seen in a patient with a high-grade and high-stage tumor. These data imply that chromatin structure changes during the progression of lung adenocarcinoma. We have therefore developed a model in which low-grade lung adenocarcinomas are linked to changes in nucleosome distributions, whereas higher-grade tumors are linked to large-scale chromosomal changes. These results provide a foundation for the development of a comprehensive framework linking the general and locus-specific roles of chromatin structure to lung cancer progression. We propose that this strategy has the potential to identify a new class of chromatin-based diagnostic, prognostic and therapeutic markers in cancer progression.     

Proteomics analysis of human serum of patients with non-small-cell lung cancer reveals proteins as diagnostic biomarker candidates

Non-small-cell lung carcinomas (NSCLC) is the most common type of lung cancer and it has a poor prognosis, because overall survival after 5 years is 20–25% for all stages. Thus, it is extremely important to increase the survival rate in the early stages NSCLC by focusing on novel screening tests of cancer identifying specific biomarkers expression associated with a more accurate tumor staging and patient prognosis. In this study, we focused our attention on quantitative proteomics of three heavily glycosylated serum proteins: AMBP, α2 macroglobulin, and SERPINA1. In particular, we analyzed serum samples from 20 NSCLC lung adenocarcinoma cancer patients in early and advanced stages, and 10 healthy donors to obtain a relative quantification through the MRM analysis of these proteins that have shown to be markers of cancer development and progression. AMBP, α2 macroglobulin, and SERPINA1 were chosen because all of them possess endopeptidase inhibitor activity and play key roles in cancer. We observe a variation in the expression of these proteins linked to the stage of the disease. Therefore, we believe that proteins like α2 macroglobulin, αmicroglobulin/bikunin, and SERPINA1 could be useful biomarkers for early detection of lung cancer and in monitoring its evolution.     

Collagen modifying enzyme P4HA1 is overexpressed and plays a role in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths globally and is histologically defined as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), with the latter accounting for 80% of all lung cancers. The 5-year overall survival rate for lung cancer patients is low as it is often discovered at advanced stages when potential cure by surgical resection is no longer an option. To identify a biomarker and target for lung cancer, we performed analysis of multiple datasets of lung cancer gene expression data. Our analyses indicated that the collagen-modifying enzyme Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is overexpressed in NSCLC. Furthermore, our investigation found that overexpression of enzymes involved in this pathway predicts poor outcome for patients with lung adenocarcinoma. Our functional studies using knockdown strategies in lung cancer cell lines in vitro indicated that P4HA1 is critical for lung cancer growth, migration, and invasion. Additionally, diethyl pythiDC (PythiDC), a small molecule inhibitor, decreased the malignant phenotypes of lung cancer cells. Moreover, we found that miR-124 regulates and targets P4HA1 in lung cancer cells. Thus, our study suggests that collagen-modifying enzymes play an important role in lung cancer aggressiveness. Furthermore, our studies showed that P4HA1 is required for lung cancer cell growth and invasion, suggesting its potential as a valid therapeutic target in lung adenocarcinoma.     

Tumor suppressor gene 14-3-3sigma is down-regulated whereas the proto-oncogene translation elongation factor 1delta is up-regulated in non-small cell lung cancers as identified by proteomic profiling

Lung cancer, a leading cause of cancer deaths, consists of two major groups: small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC) with the NSCLC accounting for approximately 75% cases of lung cancers. It has been suggested that molecular changes including overexpression of oncogenes and decreased expression of tumor suppressor genes are responsible for lung carcinogenesis. In this study, we analyzed protein profiles of four different human NSCLC cell lines compared with normal human bronchial epithelial cells using two-dimensional PAGE and MALDI-TOF mass spectrometry. We identified 12 protein spots with different expressions between the normal and cancer cells. Of these proteins, vimentin, cytokeratin 8, YB-1, PCNA, Nm23, hnRNP A2/B1, and HSP90beta were known to be up-regulated in lung cancers, which is consistent with the current study. We also found that the expression of M-type pyruvate kinase is altered in NSCLC likely due to changes in translational control and/or differential phosphorylation of the protein. Interestingly, the expression of the tumor suppressor gene 14-3-3sigma is down-regulated while that of the proto-oncogene TEF1delta is up-regulated in NSCLC cells. On the basis of these observations and previous studies, we propose that the altered expression of 14-3-3sigma and TEF1delta may be involved in lung carcinogenesis.     

Knocking down MiR-15a expression promotes the occurrence and development and induces the EMT of NSCLC cells in vitro

Non-small cell lung cancer (NSCLC) is a major type of lung cancer, with the highest mortality rate in all cancers. For all stages of NSCLC, the five-year survival is less than fifteen percent. Epithelial-mesenchymal transition (EMT) is a significant process in tumor occurrence and development, in which microRNAs may play an important role. In many cancers, microRNA-15's family member can act as suppressors or oncogenes of tumors; however, the relation between these microRNAs and EMT in lung cancer remains unclear. According to our study, miR-15a expression decreased in tumor tissues compared with than that in adjacent tissue samples. Knocking down miR-15a expression in NSCLC cells inhibited apoptosis and facilitated cell proliferation and invasion, and. Moreover, down-regulating miR-15a decreased the expression of an EMT-associated protein, E-cadherin, while increased those of vimentin, N-cadherin, and slug.     

Ornithine aminotransferase promoted the proliferation and metastasis of non-small cell lung cancer via upregulation of miR-21

The incidence and mortality of lung cancer ranked the first among all types of cancer in China, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for 85% of all lung cancers. Given that the survival rate of patients with advanced NSCLC is still poor nowadays, identification of novel therapeutic targets and the development of effective therapies are desired for the treatment of NSCLC in clinics. In this study, we reported the upregulation of ornithine aminotransferase (OAT) in NSCLC cells and clinical tumor samples as well as its association with the advanced TNM stage, metastasis, and poor tumor differentiation of lung cancer. Using different NSCLC cell lines, we demonstrated that OAT promoted the proliferation, invasion, and migration, inhibited the apoptosis, and altered cell cycle of NSCLC cells; besides, the involvement of OAT-miR-21-glycogen synthase kinase-3β signaling in the functional role of OAT in NSCLC was also revealed. Importantly, in the absence of OAT, the growth and metastasis of tumor lung cancer xenograft was significantly suppressed in the nude mice. Based on our findings, OAT may be a potential novel biomarker for the diagnosis and therapeutic outcome monitoring of NSCLC. Inhibition of OAT may also represent a new therapeutic strategy of NSCLC.     

Fn14 在 EGFR 外显子 19 缺失突变的非小细胞肺癌中的表达及其临床意义

目的:探讨成纤维细胞生长因子诱导14(Fn14)在表皮生长因子受体(EGFR)外显子19缺失的非小细胞肺癌(NSCLC)组织中的表达及其临床意义。方法:选择2010年9月至2013年11月第四军医大学唐都医院收治的125例原发性EGFR外显子19缺失的NSCLC组织及与之相对应的30例正常肺组织为研究对象,应用免疫组化法检测和比较其Fn14的表达,分析Fn14的表达与原发性EGFR外显子19缺失的的NSCLC临床病理特征的关系。结果:Fn14阳性表达主要定位于胞膜和胞质中。在125例原发性EGFR外显子19缺失的NSCLC组织中,Fn14的阳性表达率为100%,显著高于正常肺组织(P<0.001)。鳞癌和腺癌NSCLC组织中Fn14的阳性表达率比较无统计学差异(P=0.106);不同病理分化程度、不同TNM分期的NSCLC组织中Fn14的阳性表达率比较均具有显著性差异(P=0.000、P=0.000)。Fn14蛋白的表达与EGFR外显子19缺失的NSCLC的淋巴结转移状态、肿瘤大小以及肿瘤解剖学分类均显著相关(P=0.000、P=0.029、P=0.000、P=0.026),而与患者的性别、年龄、吸烟史均无关(P=0.816、P=0.122、P=0.816)。结论:Fn14在原发性EGFR外显子19缺失的NSCLC中呈异常高表达,EGFR外显子19缺失突变很可能通过上调Fn14通路,促进NSCLC的发生和发展。     

肿瘤突变特征与病理分型的关联研究

准确评估肿瘤的病理亚型对诊断、治疗和预后至关重要。以往病理亚型的诊断主要依赖HE染色法和免疫组织化学法,而随着测序技术的不断发展,对患者进行基因型和表型特点的个体分析成为可能,将肿瘤病理分型与基因分型结合用于疾病分型、诊治选择和疗效判断的精准医学研究逐渐兴起。不同病理亚型的肿瘤细胞来源、致癌因素和临床表型均不尽相同,其在基因组上会留下特异“印迹”,即突变特征。本研究通过整合癌症基因组数据库(The Cancer Genome Atlas, TCGA)中肾癌、肺癌和食管癌的外显子测序数据,分别对3种肿瘤通过肿瘤基因突变特征进行肿瘤病理分型聚类和预测。首先通过非监督聚类方法将3种肿瘤分别按照24种突变特征进行聚类分析,其次通过随机森林法从24种突变特征中进一步选择对于区分不同病理亚型有显著性的突变特征并进行聚类分析,构建突变特征对3种肿瘤病理亚型的分型模型。在肾癌中,该模型准确率达到了100% (95% confidence interval (CI): 0.93~1.00),肺癌和食管癌中分别达到了78% (95% CI: 0.66~0.86)和84% (95% CI: 0.60~0.97)。以上研究结果表明,突变特征作为新型分子标记物,对肿瘤的病理分型、诊断,尤其是早诊具有一定的参考意义。     

Effects of Multidisciplinary Team Care on the Survival of Patients with Different Stages of Non-Small Cell Lung Cancer: A National Cohort Study

In Taiwan, cancer is the top cause of death, and the mortality rate of lung cancer is the highest of all cancers. Some studies have demonstrated that multidisciplinary team (MDT) care can improve survival rates of non-small cell lung cancer (NSCLC) patients. However, no study has discussed the effect of MDT care on different stages of NSCLC. The target population for this study consisted of patients with NSCLC newly diagnosed in the 2005–2010 Cancer Registry. The data was linked with the 2002–2011 National Health Insurance Research Database and the 2005–2011 Cause of Death Statistics Database. The multivariate Cox proportional hazards model was used to explore whether the involvement of MDT care had an effect on survival. This study applied the propensity score as a control variable to reduce selection bias between patients with and without involvement of MDT care. The adjusted hazard ratio (HR) of death of MDT participants with stage III & IV NSCLC was significantly lower than that of MDT non-participants (adjusted HR = 0.87, 95% confidence interval = 0.84-0.90). This study revealed that MDT care are significantly associated with higher survival rate of patients with stage III and IV NSCLC, and thus MDT care should be used in the treatment of these patients.     

Expression of periostin in the serum of NSCLC and its function on proliferation and migration of human lung adenocarcinoma cell line (A549) in vitro

Periostin is over expressed in many epithelial malignant cancers, including lung cancer, breast cancer, ovarian cancer and colon cancer. It is related with the progression and migration of breast and ovarian cancer cells in vitro. The aim of this study was to investigate the serum level of periostin in non-small cell lung cancer (NSCLC) and its relationship with established biological and prognostic factors by enzyme-linked-immunosorbent serologic assay. We also observe the function of periostin on the proliferation and migration of human lung adenocarcinoma cell line (A549) and discuss the mechanism. The mean value for serum periostin (POSTN) was elevated in NSCLC patients (242.84 ± 5.33 pg/ml) compared to the normal healthy volunteers (215.66 ± 11.67 pg/ml) (p = 0.030). The serum level of periostin of NSCLC patients had no connection with gender, age, pathological type, TNM stage, lymph node status, tumor size and invasiveness. We constructed a plasmid named pEGFP-N1/POSTN expressing full-length human periostin. Transfecting the plasmid to A549 cells and periostin was efficiently expressed in transfected A549 cells. Our data showed that periostin could promote the proliferation and migration of A549 cells by inducing vimentin and N-cadherin expression and downregulating E-cadherin expression. These results strongly suggest that periostin is a novel molecular which play an important role during the progression and development of NSCLC.