Simultaneous off-pump myocardial revascularization and lung resection is a safe and effective treatment when unstable CHD and lung cancer coexist. In selected patients, this combined procedure may be an alternative to the two-stage approach, surgical or non-surgical (cardiologic) interventions preceding the pulmonary resection. The only statistically significant factor having an impact on long-term survival is the recurrence of the cancer.
PurposeThe aim of the project was to apply ultra-high-performance liquid chromatography–quadrupole-Orbitrap-high-resolution mass spectrometry for serum metabolite profiling of non-small-cell lung cancer (NSCLC). This Orbitrap-based methodology has been applied for a study of NSCLC potential markers for the first time.MethodsAfter extraction using protein precipitation, sera were separated on the ACE Excel 2 C18-PFP (100 × 2.1 mm, 2.0 µm) column using gradient elution and analyzed within the range of 70–1000 m/z. Only patients with early stage disease (stages IA–IIB) were included in the study, providing opportunity to find biomarkers for early lung cancer detection. The resulting metabolite profiles were subjected to univariate and multivariate statistical tests.Results36 features were found significantly changed between NSCLC group and controls after FDR adjustment and 19 were identified using various metabolite databases (in-house library, HMDB, mzCloud). The study revealed a number of NSCLC biomarker candidates which belong to such compound classes as acylcarnitines, organic acids, and amino acids. Multivariate ROC curve built using 12 identified metabolites was characterized by AUC = 0.836 (0.722–0.946). There were no significant differences in the serum metabolite profiles between two most common histological types of lung cancer—adenocarcinoma and squamous cell carcinoma.ConclusionsThrough identification of novel potential tumor markers, Orbitrap-based global metabolic profiling is a useful strategy in cancer research. Our study can accelerate development of new diagnostic and therapeutic strategies in NSCLC. The metabolites involved in discrimination between NSCLC patients and the control subjects should be further explored using a targeted approach.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-017-2347-0) contains supplementary material, which is available to authorized users.
The ability of early lung cancer diagnosis is an unmet need in clinical practice. Lung cancer metabolomic analyses conducted so far have demonstrated several abnormalities in cancer lipid profile providing a rationale for further study of blood lipidome of the patients. In the present research, we performed a targeted lipidome screening to select molecules that show promise for early lung cancer detection. The study was conducted on serum samples collected from newly diagnosed, stage I non-small cell lung cancer (NSCLC) patients and non-cancer controls. A high-throughput mass spectrometry-based platform with confirmed interlaboratory reproducibility was used. The analyzed profile consisted of acylcarnitines, sphingomyelins, phosphatidylcholines and lysophosphatidylcholines. Among the assayed lipid species, the significant differences between NSCLC and non-cancer subjects were observed in the group of phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPC), especially in the levels of lysoPC a C26:0; lysoPC a C26:1; PC aa C42:4; and PC aa C34:4. The metabolites mentioned above were used to create a multivariate classification model, which reliability was proved by permutation tests as well as external validation. Our study indicated choline-containing phospholipids as potential lung cancer markers. Further investigations of phospholipidome are crucial to better describe the shifts in metabolite composition occurring in lung cancer patients.Electronic supplementary materialThe online version of this article (10.1007/s10238-019-00566-7) contains supplementary material, which is available to authorized users.
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