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Abstract：
Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway. In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC.
UNASSIGNED: Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)).
UNASSIGNED: Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)).
摘要：
肺癌（LC）和慢性阻塞性肺疾病（COPD）通常在吸烟者中共存，COPD的存在会增加发生LC的风险。这项研究的目的是鉴定能够区分这两种病理实体的不同蛋白质组学图谱。在分为四组的60名患者的支气管肺泡灌洗（BAL）中评估了蛋白质含量：COPD，COPD和LC，LC无COPD,并且既不使用COPD也不使用LC进行控制。通过二维聚丙烯酰胺凝胶电泳（2D-PAGE）将蛋白质分离成点，并通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF/TOF）进行检查。与对照组相比，LC和/或COPD组总共有40种蛋白质差异表达。对每个病理实体(LC和COPD)鉴定和验证不同的蛋白质谱。涉及的主要网络与炎症信号有关，自由基清除和氧化应激反应，糖酵解和糖异生途径。LC和COPD之间最相关的信号联系是通过NF-κB途径。总之,鉴定的蛋白质谱有助于阐明这两种疾病的潜在致病途径，并为早期诊断LC提供潜在的生物标志物新工具。
■序列覆盖。通过来自所鉴定的具有大于或等于95%的置信度的肽的匹配氨基酸的百分比除以序列中氨基酸的总数来估计特定蛋白质的蛋白质序列覆盖率(95%)。独创性途径分析。将我们的蛋白质映射到生物学途径和疾病网络上，表明22种蛋白质与炎症信号相关（p值：1.3510（-08）-1.4210（-02）），15种蛋白质与自由基清除和氧化应激反应相关（p值：4.9310（-11）-1.2710（-02）），和9个蛋白与糖酵解和糖异生途径有关（p值：7.3910（-09）-1.5810（-02））。
■序列覆盖。通过来自所鉴定的具有大于或等于95%的置信度的肽的匹配氨基酸的百分比除以序列中氨基酸的总数来估计特定蛋白质的蛋白质序列覆盖率(95%)。独创性途径分析。将我们的蛋白质映射到生物学途径和疾病网络上，表明22种蛋白质与炎症信号相关（p值：1.3510（-08）-1.4210（-02）），15种蛋白质与自由基清除和氧化应激反应相关（p值：4.9310（-11）-1.2710（-02）），和9个蛋白与糖酵解和糖异生途径有关（p值：7.3910（-09）-1.5810（-02））。
