The high prevalence of lung cancer (LC) has triggered the search of biomarkers for early diagnosis of this disease. For this purpose the study of metabolic changes related to the development of lung cancer could provide interesting information about its early diagnosis. In this sense, chronic obstructive pulmonary disease (COPD), a disease associated with tumor development, is a comorbidity that increases the risk of onset and progression of lung neoplasia and has also to be considered in the study of pathology related to lung cancer. This work develop a metabolomic approach based on direct infusion mass spectrometry using a hybrid triple quadrupole-time of flight mass spectrometer (DI-ESI-QqQ-TOF-MS) in order to identify altered metabolites from serum of LC and COPD patients and evaluate its relationship and implication in the progression of LC. This methodology has been applied to 30 serum samples from LC, 30 healthy patients used as controls (HC) and 30 serum samples from COPD to found altered metabolites from both LC and COPD diseases. In addition, some metabolic differences and similarities were found in Pulmonary Emphysema and Chronic Bronchitis patients. On the other hand, altered metabolites were studied in different stages of LC (II, III and IV) to evaluate the perturbation of them throughout the progression of disease. The sample treatment consisted of the extraction of polar and non-polar metabolites from serum that was later infused into the mass spectrometer using an electrospray ionization source in positive and negative mode. Partial least squares discriminant analysis (PLS-DA) allowed a classification between LC, HC and COPD groups in all acquisition modes. A total of 35 altered and common metabolites between LC and COPD, including amino acids, fatty acids, lysophospholipids, phospholipids and triacylglycerides were identified, being alanine, aspartate and glutamate metabolism the most altered. Finally, ROC curves were applied to the dataset and metabolites with AUC value higher than 0.70 were considered as relevant in the progression of LC.

肺癌（LC）的高发病率引发了对生物标记物的搜寻，以期对该疾病的早期诊断。为此目的，与肺癌的发展有关的代谢变化的研究可以提供有关其早期诊断的有趣信息。从这个意义上说，慢性阻塞性肺疾病（COPD）是一种与肿瘤发展有关的疾病，是一种合并症，会增加肺癌发生和发展的风险，并且在与肺癌相关的病理研究中也必须考虑到这一点。这项工作基于混合三重四极杆飞行时间质谱仪（DI-ESI-QqQ-TOF-MS）的直接输注质谱法，开发了一种代谢组学方法，以便从LC和COPD患者的血清中鉴定出改变的代谢物并对其进行评估LC进程中的关系和含义。该方法已应用于LC的30个血清样本，用作对照（HC）的30例健康患者和COPD的30个血清样本，以发现LC和COPD疾病的代谢物发生改变。此外，在肺气肿和慢性支气管炎患者中发现了一些代谢差异和相似性。另一方面，在LC的不同阶段（II，III和IV）对改变的代谢产物进行了研究，以评估它们在疾病发展过程中的扰动。样品处理包括从血清中提取极性和非极性代谢物，然后使用电喷雾电离源以正负模式将其注入质谱仪中。偏最小二乘判别分析（PLS-DA）允许在所有采集模式下对LC，HC和COPD组进行分类。LC和COPD之间共有35种改变的和常见的代谢产物，包括氨基酸，脂肪酸，溶血磷脂，磷脂和三酰基甘油酯，其中丙氨酸，天冬氨酸和谷氨酸的代谢变化最大。最后，将ROC曲线应用于数据集，并认为AUC值高于0.70的代谢物与LC的进展相关。