支气管肺泡灌洗在肺部真菌感染中的诊断价值

近年来,肺部真菌感染的发病率不断增加,尽管培养是真菌诊断的金标准,但其耗时较长,临床应用受限。支气管镜下肺泡灌洗技术方便、快捷、创伤小,通过对应用该技术所获得的支气管肺泡灌洗液行细胞学检查、常规染色、真菌抗原和分子学技术检测已是快速诊断某些真菌感染的重要手段之一。     

肿瘤自身抗体检测对早期肺癌的诊断价值

目的探讨肺癌自身抗体P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1和CAGE对早期肺癌的诊断价值。方法采用ELISA法检测肺癌组(46例首次确诊的肺癌患者)和对照组(包含22名肺部良性疾病患者及23例健康体检者)血清中肺癌自身抗体P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1和CAGE表达水平,分析评价7种肺癌自身抗体单独检测和联合检测对肺癌的临床诊断价值。结果肺癌组患者血清中7种自身抗体的水平明显高于对照组(均P<0.05)。肺癌组患者7种抗体联合检测的阳性率明显高于对照组(65.22%vs 15.56%,χ²=23.252,P<0.001)。单一肺癌自身抗体检测的敏感性为4.35%~36.96%,特异性为93.30%~100.00%,AUC为0.695~0.832。7种肺癌抗体联合检测的敏感性为65.22%,特异性为84.44%,AUC为0.897。结论早期肺癌患者血清中7种肺癌自身抗体水平均较高。单一肺癌自身抗体检测的特异性较高,但敏感性较低。7种肺癌自身抗体联合检测具有较高的敏感性,可成为临床早期肺癌新的辅助诊断指标。     

支气管肺泡灌洗液G试验可有效诊断早产儿肺部侵袭性真菌感染

本研究试图通过测量血清与支气管肺泡灌洗液中1,3-β-D葡聚糖浓度,分析应用支气管肺泡灌洗液G试验作为早期诊断早产儿肺部侵袭性真菌感染的可行性。选取2014年2月至2016年9月经确诊为侵袭性真菌感染的早产患儿42例作为观察组,将同期生产于我院的健康早产儿61例作为对照组。在清晨时间采集观察组与对照组早产儿的静脉血与分支气管肺泡灌洗液,将静脉血离心取上层血清待用,比较血清与支气管肺泡灌洗液的G试验的表达情况、阳性率及灵敏性。观察组早产儿经测量后,支气管肺泡灌洗液以及血浆中的1,3-β-D葡聚糖水平与健康早产儿比较有差异,说明通过G实验检测1,3-β-D葡聚糖有诊断早产儿侵袭性真菌感染的价值;观察组早产儿的支气管肺泡灌洗液G试验阳性率为83.33%,血浆G试阳性率为64.29%,x~2值为3.941,p值为0.047;支气管肺泡灌洗液G试验灵敏度为89.47%,血浆G试验灵敏度为65.79%,二者x~2值为6.138,p值为0.013。本研究的结果认为支气管肺泡灌洗液G试验可以有效、敏感的测定早产儿体内1,3-β-D葡聚糖的表达情况,应用于早产儿早期诊断肺部侵袭性真菌感染具有临床价值。     

炎症因子在大叶性肺炎患儿支气管肺泡灌洗液及血清中的表达及临床意义

目的:探讨炎症因子在大叶性肺炎患儿支气管肺泡灌洗液及血清中的表达水平及其临床意义。方法:收集2014年6月至2016年6月我院儿科收治的79例大叶性肺炎患儿为病例组,按照临床肺部感染评分(CPIS)分为重度组(n=46)和轻度组(n=33),于同期随机选取30例健康儿童为对照组,采用双抗体夹心酶联免疫吸附法(ELISA)检测各组支气管肺泡灌洗液及血清炎症因子如白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-17(IL-17)、肿瘤坏死因子(TNF-α)以及高迁移率族蛋白B1(HMGB1)表达水平。结果:重度组、轻度组血清IL-6、IL-8、IL-17、TNF-α及HMGB1水平高于对照组,重度组血清IL-6、IL-8、IL-17、TNF-α及HMGB1水平高于轻度组,差异有统计学意义(P0.05)。病例组患儿支气管肺泡灌洗液IL-6、IL-8、IL-17、TNF-α及HMGB1水平高于血清,差异有统计学意义(P0.05)。重度组、轻度组支气管肺泡灌洗液IL-6、IL-8、IL-17、TNF-α及HMGB1水平高于血清,差异有统计学意义(P0.05),重度组支气管肺泡灌洗液、血清IL-6、IL-8、IL-17、TNF-α及HMGB1水平分别高于轻度组,差异有统计学意义(P0.05)。经Spearman积矩相关分析,支气管肺泡灌洗液与血清中IL-6、IL-8、IL-17、TNF-α及HMGB1水平分别呈正相关关系(r=0.711、0.695、0.752、0.793、0.728,P0.05)。结论:炎症因子在大叶性肺炎患儿支气管肺泡灌洗液及血清中呈高表达,并与大叶性肺炎病情严重程度密切相关,联合检测有助于早期评估病情。     

磷脂酶D缺失对小鼠抗烟曲霉感染过程的影响研究

目的揭示宿主磷脂酶D(phospholipase D,PLD)应对烟曲霉感染过程中的重要作用和可能机制。方法应用滴鼻方式使野生小鼠和磷脂酶D双基因敲除小鼠(pld1~(-/-)pld2~(-/-))感染烟曲霉孢子后,取小鼠肺组织、抽取支气管肺泡灌洗液,应用组织匀桨与菌落计数的方法检测小鼠肺组织中烟曲霉负荷,采用eBioscience公司的多因子检测试剂盒检测肺泡灌洗液中炎症因子分泌情况;分离两种小鼠的骨髓细胞并诱导分化为成熟巨噬细胞(BMDM),制霉菌素法检测其吞噬和杀死烟曲霉孢子的能力。结果感染烟曲霉孢子6 h后,pld1~(-/-)pld2~(-/-)小鼠肺部真菌负荷显著高于野生小鼠,其肺泡灌洗液和肺泡巨噬细胞中均存在大量孢子,肺泡灌洗液中炎症因子浓度显著升高;体外实验证明pld1~(-/-)pld2~(-/-)小鼠的BMDM细胞吞噬和杀死烟曲霉孢子的能力显著减弱。结论小鼠pld1基因和pld2基因同时敲除导致其巨噬细胞的吞噬和杀死烟曲霉孢子的能力显著减弱,进而可能降低小鼠抗烟曲霉感染的能力。同时机体可能通过分泌大量的炎症因子以招募其他免疫细胞杀灭烟曲霉孢子。     

肺炎支原体感染鼠P1特异抗原的动态检测

通过实验动物模型探讨肺炎支原体感染动物肺泡灌洗液中特异抗原检出率的动态变化,为肺炎支原体感染的临床诊断提供理论依据。小鼠经鼻自然感染肺炎支原体,分别采集感染后不同时间点小鼠的支气管灌洗液,应用量子点标记肺炎支原体P1蛋白抗体,直接免疫荧光法检测感染鼠肺泡灌洗液中肺炎支原体P1特异抗原,同时通过PCR检测肺组织肺炎支原体DNA及肺组织病理切片观察肺部炎性变化确定小鼠感染。结果显示,感染鼠肺炎支原体特异抗原在感染后第3天检出阳性率为75%,第7天达高峰为83%,之后随病程延长,抗原检测的阳性率逐渐下降,在感染后第14、21天检出阳性率分别为58%和25%。肺炎支原体特异抗原在感染早期检出率高。应用量子点标记肺炎支原体P1蛋白抗体,直接免疫荧光法检测肺炎支原体特异抗原可应用于肺炎支原体感染的早期诊断。     

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。     

小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸治疗特发性肺纤维化的临床疗效分析

目的:观察小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸对特发性肺纤维化(IPF)患者肺功能及支气管肺泡灌洗液炎症因子表达的影响。方法:随机将56例确诊为IPF的住院患者分为对照组和治疗组,对照组给予常规治疗,吸氧,戒烟,吸入布地奈德及乙酰半胱氨酸;治疗组在常规治疗基础上加服小剂量阿奇霉素片。动态观察两组患者治疗3、6个月的疗效及肺功能的改善情况;完成2个疗程(6个月)治疗后,检测和比较两组支气管肺泡灌洗液相关炎症因子水平的变化。结果:治疗3个月时,两组患者的动脉血氧分压(PO2)、肺活量(VC)、1秒钟用力呼气容积占预计值百分比(FEV1%pred)、最大通气量占预计值百分比(MVV%pred)、单位肺泡容积的一氧化碳弥散量占预计值百分比(DLCO/VA%pred)均较治疗前显著增加(P0.05);治疗6个月时,治疗组的有效率(20/26,76.9%)明显高于对照组(14/30,46.7%),且PO2、VC、FEV1%pred、MVV%pred及DLCO/VA%pred等肺功能指标均显著高于对照组(P0.05);对照组支气管肺泡灌洗液TNF-α、IL-8浓度均较治疗前降低(P0.05),IL-4、IL-10、IFN-γ浓度较治疗前无明显变化;而治疗组支气管肺泡灌洗液TNF-α、IL-8、IL-4、IL-10浓度均较治疗前降低,IFN-γ浓度较治疗前明显增加(P0.05)。结论:阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸可能通过改变支气管肺泡灌洗液IFN-γ等炎症因子浓度有效改善IPF患者的肺功能。     

142例支气管肺泡灌洗液真菌免疫荧光染色检测结果与G/GM试验结果对比分析

目的探讨真菌免疫荧光染色检测支气管肺泡灌洗液(brondioalveolar lavage fluid,BALF)在肺部真菌感染诊断中的意义。方法对2019年1月至12月送检至本所的142例BALF标本进行G/GM试验及真菌免疫荧光染色检测。结果142例BALF中免疫荧光染色检测阳性为52例(占36.62%),G试验同时阳性者为49例,GM试验同时阳性者为11例。免疫荧光染色检测阳性例数与KOH湿片镜检阳性27例(占19.01%)比较检出率明显提高。结论真菌免疫荧光染色检测作为一种快速方便高效直观的真菌常规检测方法,是BALF标本中真菌检测的1个重要补充,为临床肺部真菌感染的诊断提供了1种快速检测方法。     

应用双向热循环消减SELEX技术筛选肺癌血清核酸适配体

肺癌是发病率和死亡率较高的恶性肿瘤。现阶段,用于肺癌早期诊断的血清肿瘤标志物因其特异性与敏感性均较低,严重影响肺癌的临床诊断和治疗。本文用双向热循环消减指数富集的配基进化(systematic evolution of ligands by exponential enrichment, SELEX)技术,筛选肺癌和非癌血清标志物的核酸适配体,建立肺癌的检测方法,提高诊断和治疗效率。实验用环氧基琼脂磁珠为筛选介质,以非癌混合血清、肺癌混合血清作为双向靶标。应用热循环消减SELEX技术,经19轮筛选分别获得非癌和肺癌血清的特异性核酸适配体。通过高通量测序,得到 40条非癌核酸适配体序列和 41条肺癌核酸适配体序列。从肺癌与非癌血清特异性核酸适配体序列中分别挑选出高丰度的 4条序列,合成后制成检测试剂,经临床血清验证,阳性率为 90%。该检测方法检测灵敏度高,为肺癌的早期诊断和治疗提供了新的分子识别元件。     

Lipid analysis of bronchoalveolar lavage fluid (BAL) by MALDI-TOF mass spectrometry and 31P NMR spectroscopy

Despite the high clinical relevance, only the cellular moiety of bronchoalveolar lavage (BAL) has been intensively investigated and is used for diagnosis purposes. On the other hand, the cell-free fluid is, by far, less characterized. Although this fluid represents a relatively simple mixture of only a few different phospholipids (mainly phosphatidylcholine, phosphatidylglycerol and cholesterol), methods for the routine analysis of these fluids are still lacking. In the present investigation we have applied, for the first time, MALDI-TOF mass spectrometry, as well as 31P NMR spectroscopy to the analysis of organic extracts of bronchoalveolar lavage fluids. BAL from different mammals (rat, minipig, rabbit and man) were investigated and, for means of comparison, organic extracts of lung tissue were also examined. Both applied methods provide fast and reliable information on the lipid composition of the bronchoalveolar lavage. However, despite of its comparably low sensitivity, 31P NMR spectroscopy detects all phospholipid species in a single experiment and with the same sensitivity, whereas MALDI-TOF fails in the detection of phosphatidylethanolamine in the presence of higher quantities of phosphatidylcholine. In contrast, MALDI-TOF mass spectrometry is more suitable for the detection of cholesterol and the determination of the fatty acid composition of the individual phospholipids, especially lysolipids. It will be shown that all BALs exhibit significant, species-dependent differences that mainly concern the content of phosphatidylglycerol and lyso-phosphatidylcholine. It is concluded that both methods are suitable tools in lipid research due to the (in comparison to alternative methods) simplicity of performance.     

Improved Classification of Lung Cancer Using Radial Basis Function Neural Network with Affine Transforms of Voss Representation

Lung cancer is one of the diseases responsible for a large number of cancer related death cases worldwide. The recommended standard for screening and early detection of lung cancer is the low dose computed tomography. However, many patients diagnosed die within one year, which makes it essential to find alternative approaches for screening and early detection of lung cancer. We present computational methods that can be implemented in a functional multi-genomic system for classification, screening and early detection of lung cancer victims. Samples of top ten biomarker genes previously reported to have the highest frequency of lung cancer mutations and sequences of normal biomarker genes were respectively collected from the COSMIC and NCBI databases to validate the computational methods. Experiments were performed based on the combinations of Z-curve and tetrahedron affine transforms, Histogram of Oriented Gradient (HOG), Multilayer perceptron and Gaussian Radial Basis Function (RBF) neural networks to obtain an appropriate combination of computational methods to achieve improved classification of lung cancer biomarker genes. Results show that a combination of affine transforms of Voss representation, HOG genomic features and Gaussian RBF neural network perceptibly improves classification accuracy, specificity and sensitivity of lung cancer biomarker genes as well as achieving low mean square error.     

Detection of K-ras and p53 mutations in sputum samples of lung cancer patients using laser capture microdissection microscope and mutation analysis

Mutations in the p53 tumor suppressor gene and the K-ras oncogene have been frequently found in sputum and bronchoalveolar lavage (BAL) samples of lung cancer patients and other patients prior to presenting clinical symptoms of lung cancer, suggesting that they may provide useful biomarkers for early lung cancer diagnosis. However, the detection of these gene mutations in sputum and BAL samples has been complicated by the fact that they often occur in only a small fraction of epithelial cells among sputum cells and, in the case of p53 gene, at many codons. In this study, sputum cells were collected on a filter membrane by sputum cytocentrifugation and morphologically analyzed. Epithelial cells were selectively taken by using a laser capture microdissection microscope and analyzed by polymerase chain reaction (PCR) and single-stranded conformational polymorphism (SSCP) for p53 mutations and by PCR and denaturing gradient gel electrophoresis (DGGE) for K-ras mutations. This method was used to analyze sputum of 15 Chinese women with lung cancer from Xuan Wei County, China and detected mutations in sputum of 7 (46.7%) patients, including 5 patients with p53 mutations, 1 patient with a K-ras mutation, and 1 patient with K-ras and p53 mutations. For comparison, only two of the mutations were detected by conventional methods. Therefore, the laser capture/mutation analysis method is sensitive and facilitates the detection of low-fraction mutations occurring throughout the p53 and K-ras genes in sputum of lung cancer patients. This method may be applicable to the analysis of epithelial cells from clinically normal sputum or BAL samples from individuals with a high risk for developing lung cancer.     

Pneumocystis carinii pneumonia: detection of parasites in sputum and bronchoalveolar lavage fluid by monoclonal antibodies.

Diagnosis of pneumocystis pneumonia is based on identifying Pneumocystis carinii cytochemically in material from the lung. The silver methenamine staining methods most commonly used are technically difficult and lack specificity. The diagnostic value of immunocytological identification of the parasite was evaluated by using mouse monoclonal antibody 3F6, specific for human pneumocystis, to identify P carinii in bronchoalveolar lavage fluid and sputum by immunofluorescence and was compared with that of other variables. Bronchoalveolar lavage was performed on 25 patients positive for HIV antibody with clinically suspected pneumocystis pneumonia and 40 patients negative for HIV antibody who presented with interstitial disorders of the lung. Lavage fluid showed pneumocystis only in the patients positive for antibody, the parasite being detected in 19 by immunofluorescence and in 17 by a modified silver methenamine staining method. Chest x ray films obtained at the time of bronchoscopy showed interstitial or alveolar shadowing in 17 of the 19 patients, but clinical symptoms and the presence of antibodies to pneumocystis did not seem to be predictive. Sputum samples were collected during 43 episodes of clinically suspected pneumocystis pneumonia in patients positive for HIV antibody. Pneumocystis was detected consistently more commonly by immunofluorescence than the silver strain in sputum collected routinely and induced by inhalation of saline. In 17 patients bronchoalveolar lavage followed sputum collection, and the sensitivity of detection of pneumocystis in immunofluorescence in sputum compared with lavage fluid was 57% (8/14). Immunofluorescence was suitable for specimens fixed in ethanol and seemed highly specific and more sensitive than the standard cytochemical methods for identifying pneumocystis.     

A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer

The early detection of lung cancer is a major clinical challenge. Long noncoding RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly released from primary tumors or the circulating cancer cells might provide cell-free cancer biomarkers. The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer–associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls. In the development cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and RMRP) displayed a considerably high plasma level in lung cancer patients vs. cancer-free controls (all P?<?.001). Combined use of the plasma lncRNAs as a biomarker signature produced 84.13% sensitivity and 87.88% specificity for diagnosis of lung cancer, independent of stage and histological type of lung tumor, and patients' age and sex (all P?>?.05). The diagnostic value of the plasma lncRNA signature for lung cancer early detection was confirmed in the validation cohort. The plasma lncRNA signature may provide a potential blood-based assay for diagnosing lung cancer at the early stage. Nevertheless, a prospective study is warranted to validate its clinical value.     

Effect of adenosine A2A receptor activation in murine models of respiratory disorders

Activation of the adenosine A(2A) receptor has been postulated as a possible treatment for lung inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). In this report, we have studied the anti-inflammatory properties of the reference A(2A) agonist CGS-21680, given intranasally at doses of 10 and 100 microg/kg, in a variety of murine models of asthma and COPD. After an acute ovalbumin challenge of sensitized mice, prophylactic administration of CGS-21680 inhibited the bronchoalveolar lavage fluid inflammatory cell influx but not the airway hyperreactivity to aerosolized methacholine. After repeated ovalbumin challenges, CGS-21680 given therapeutically inhibited the bronchoalveolar lavage fluid inflammatory cell influx but had no effect on the allergen-induced bronchoconstriction, the airway hyperreactivity, or the bronchoalveolar lavage fluid mucin levels. As a comparator, budesonide given intranasally at doses of 0.1-1 mg/kg fully inhibited all the parameters measured in the latter model. In a lipopolysaccharide-driven model, CGS-21680 had no effect on the bronchoalveolar lavage fluid inflammatory cell influx or TNF-alpha, keratinocyte chemoattractant, and macrophage inflammatory protein-2 levels, but potently inhibited neutrophil activation, as measured by bronchoalveolar lavage fluid elastase levels. With the use of a cigarette smoke model of lung inflammation, CGS-21680 did not significantly inhibit bronchoalveolar lavage fluid neutrophil infiltration but reversed the cigarette smoke-induced decrease in macrophage number. Together, these results suggest that activation of the A(2A) receptor would have a beneficial effect by inhibiting inflammatory cell influx and downregulating inflammatory cell activation in asthma and COPD, respectively.     

Sputum analysis: Non‐invasive early lung cancer detection

Lung cancer is the leading cause of cancer‐related deaths over the world, characterized by a very high mortality rate. Molecular technique development tries to focus on early detection of cancers by studying molecular alterations that characterize cancer cells. Worldwide lung cancer research has focused on an ever‐increasing number of molecular elements of carcinogenesis at genetic, epigenetic and protein levels. The non‐invasiveness is the characteristic that all clinical trials on cancer detection should have. Abnormal chest imaging and/or non‐specific symptoms are initial signals of lung cancer that appear in an advanced stage of disease. This fact represents the cause of the low 5‐year survival rate: over 90% of patients dying within 5 years of diagnosis. Since smokers have higher quantity of sputum containing exfoliated cells from the bronchial tree, and the sputum represents the most easily accessible biological fluid and its collection is non‐invasive, analysis of this sample represents a good area of research in early lung cancer diagnosis. Continued cigarette smoking is the cause of chronic obstructive pulmonary disease (COPD), with an estimated attributable risk factor exceeding 80% in smoking affected individuals. Lung cancer is found in 40–70% of patients with COPD, particularly in severe disease, and it is a common cause of death in these patients. A large prospective trial of almost half a million non‐smokers showed as lung cancer is also common in patients with COPD who have never smoked. This review describes issues related to early lung cancer screening using non‐invasive methods. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.     

Protein profiling in respiratory disease: techniques and impact

Multifactorial diseases such as respiratory disease call for a global analysis of such disorders. Recent advances in protein profiling techniques may allow for early diagnosis of respiratory disease, which is crucial for intervention and treatment. In order to reduce false-positive rates, clinical diagnosis requires a high degree of sensitivity and specificity to be an effective screening tool. Protein profiles identified by ProteinChip^® (Ciphergen Biosystems) technology coupled with mass spectrometry affords a global analysis of clinical samples and is beginning to reach acceptable levels of sensitivity and specificity. Combining the profile with another diagnostic tool enhances the effectiveness of protein profiles to classify disease. Although current efforts have centered on serum protein profiling, the local environment of the lung may be better reflected in proteins of bronchoalveolar lavage or sputum. Identification of biomarkers of disease by protein profiling anaylses may lead to an understanding of the mechanisms of this disease and contribute to the discovery of new therapeutics for the prevention and treatment of disease. Advancing these analyses are techniques such as ProteinChip mass spectrometry, laser capture microdissection, tissue microarrays and fluorescently labeled antibody bead arrays, which enable the direct global analysis of complex mixtures. Effective high-throughput and ease of use of clinical testing will arrive with improvements in bioinformatics and decreases in instrumentation costs.     

Protein profiling in respiratory disease: techniques and impact

Multifactorial diseases such as respiratory disease call for a global analysis of such disorders. Recent advances in protein profiling techniques may allow for early diagnosis of respiratory disease, which is crucial for intervention and treatment. In order to reduce false-positive rates, clinical diagnosis requires a high degree of sensitivity and specificity to be an effective screening tool. Protein profiles identified by ProteinChip (Ciphergen Biosystems) technology coupled with mass spectrometry affords a global analysis of clinical samples and is beginning to reach acceptable levels of sensitivity and specificity. Combining the profile with another diagnostic tool enhances the effectiveness of protein profiles to classify disease. Although current efforts have centered on serum protein profiling, the local environment of the lung may be better reflected in proteins of bronchoalveolar lavage or sputum. Identification of biomarkers of disease by protein profiling analyses may lead to an understanding of the mechanisms of this disease and contribute to the discovery of new therapeutics for the prevention and treatment of disease. Advancing these analyses are techniques such as ProteinChip mass spectrometry, laser capture microdissection, tissue microarrays and fluorescently labeled antibody bead arrays, which enable the direct global analysis of complex mixtures. Effective high-throughput and ease of use of clinical testing will arrive with improvements in bioinformatics and decreases in instrumentation costs.     

DNA Methylation Markers in Lung Cancer

Lung cancer is the most common cancer and the leading cause of cancer-related morbidity and mortality worldwide. As early symptoms of lung cancer are minimal and non-specific, many patients are diagnosed at an advanced stage. Despite a concerted effort to diagnose lung cancer early, no biomarkers that can be used for lung cancer screening and prognosis prediction have been established so far. As global DNA demethylation and gene-specific promoter DNA methylation are present in lung cancer, DNA methylation biomarkers have become a major area of research as potential alternative diagnostic methods to detect lung cancer at an early stage. This review summarizes the emerging DNA methylation changes in lung cancer tumorigenesis, focusing on biomarkers for early detection and their potential clinical applications in lung cancer.