Biomarkers for Lung Cancer Screening and Detection

Serum metabolome is a promising source of molecular biomarkers that could support early detection of lung cancer in screening programs based on low-dose computed tomography. Several panels of metabolites that differentiate lung cancer patients and healthy individuals were reported, yet none of them were validated in the population at high-risk of developing cancer. Here we analyzed serum metabolome profiles in participants of two lung cancer screening studies: MOLTEST-BIS (Poland, n = 369) and SMAC-1 (Italy, n = 93). Three groups of screening participants were included: lung cancer patients, individuals with benign pulmonary nodules, and those without any lung alterations. Concentrations of about 400 metabolites (lipids, amino acids, and biogenic amines) were measured by a mass spectrometry-based approach. We observed a reduced level of lipids, in particular cholesteryl esters, in sera of cancer patients from both studies. Despite several specific compounds showing significant differences between cancer patients and healthy controls within each study, only a few cancer-related features were common when both cohorts were compared, which included a reduced concentration of lysophosphatidylcholine LPC (18:0). Moreover, serum metabolome profiles in both noncancer groups were similar, and differences between cancer patients and both groups of healthy participants were comparable. Large heterogeneity in levels of specific metabolites was observed, both within and between cohorts, which markedly impaired the accuracy of classification models: The overall AUC values of three-state classifiers were 0.60 and 0.51 for the test (MOLTEST) and validation (SMAC) cohorts, respectively. Therefore, a hypothetical metabolite-based biomarker for early detection of lung cancer would require adjustment to lifestyle-related confounding factors that putatively affect the composition of serum metabolome.

Section: Introductionmentioning

confidence: 99%

Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts

Widłak

Jelonek

Kurczyk

et al. 2021

“…Potential biomarkers for early lung cancer can be found in various biological fluids; however, blood is the richest and most readily available source [ 10 , 11 ]. Candidates for such biomarkers include serum proteins, free nucleic acids, and metabolites [ 11 , 12 ]. Several works reported serum/plasma proteins, which levels are associated with the risk of lung cancer [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…More recently, serum metabolites and lipids have emerged as another class of potential biomarkers in lung cancer [ 16 , 17 ]. Several other review papers could be suggested that cover this well-researched field [ 11 , 12 , 13 , 18 , 19 , 20 , 21 ]. However, though numerous biomarker candidates have been proposed only a few of them have been positively validated in the proper clinical settings.…”

Section: Introductionmentioning

confidence: 99%

Serum Exosomes and Their miRNA Load—A Potential Biomarker of Lung Cancer

Smolarz

Widłak

2021

Early detection of lung cancer in screening programs is a rational way to reduce mortality associated with this malignancy. Low-dose computed tomography, a diagnostic tool used in lung cancer screening, generates a relatively large number of false-positive results, and its complementation with molecular biomarkers would greatly improve the effectiveness of such programs. Several biomarkers of lung cancer based on different components of blood, including miRNA signatures, were proposed. However, only a few of them have been positively validated in the context of early cancer detection yet, which imposes a constant need for new biomarker candidates. An emerging source of cancer biomarkers are exosomes and other types of extracellular vesicles circulating in body fluids. Hence, different molecular components of serum/plasma-derived exosomes were tested and showed different levels in lung cancer patients and healthy individuals. Several studies focused on the miRNA component of these vesicles. Proposed signatures of exosome miRNA had promising diagnostic value, though none of them have yet been clinically validated. These signatures involved a few dozen miRNA species overall, including a few species that recurred in different signatures. It is worth noting that all these miRNA species have cancer-related functions and have been associated with lung cancer progression. Moreover, a few of them, including known oncomirs miR-17, miR-19, miR-21, and miR-221, appeared in multiple miRNA signatures of lung cancer based on both the whole serum/plasma and serum/plasma-derived exosomes.

“…Blood is the most widely available source of biomarkers potentially enhancing the power of early lung cancer detection or discrimination of lung nodules. Several components of blood, including circulating tumor cells, circulating tumor DNA, microRNA, autoantibodies, and specific serum/plasma proteins, have been analyzed in the search for such biomarkers [ 7 , 8 , 9 , 10 ], but none have been widely adopted in clinics yet. Moreover, serum metabolome represents a novel potential source of cancer markers, and a few large studies revealed sets of metabolites whose serum/plasma levels discriminated lung cancer patients from matched controls [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Lipid Composition of Serum-Derived Small Extracellular Vesicles in Participants of a Lung Cancer Screening Study

Smolarz

Kurczyk

Jelonek

et al. 2021

Molecular components of exosomes and other classes of small extracellular vesicles (sEV) present in human biofluids are potential biomarkers with possible applicability in the early detection of lung cancer. Here, we compared the lipid profiles of serum-derived sEV from three groups of lung cancer screening participants: individuals without pulmonary alterations, individuals with benign lung nodules, and patients with screening-detected lung cancer (81 individuals in each group). Extracellular vesicles and particles were purified from serum by size-exclusion chromatography, and a fraction enriched in sEV and depleted of low-density lipoproteins (LDLs) was selected (similar sized vesicles was observed in all groups: 70–100 nm). The targeted mass-spectrometry-based approach enabled the detection of 352 lipids, including 201 compounds used in quantitative analyses. A few compounds, exemplified by Cer(42:1), i.e., a ceramide whose increased plasma/serum level was reported in different pathological conditions, were upregulated in vesicles from cancer patients. On the other hand, the contribution of phosphatidylcholines with poly-unsaturated acyl chains was reduced in vesicles from lung cancer patients. Cancer-related features detected in serum-derived sEV were different than those of the corresponding whole serum. A high heterogeneity of lipid profiles of sEV was observed, which markedly impaired the performance of classification models based on specific compounds (the three-state classifiers showed an average AUC = 0.65 and 0.58 in the training and test subsets, respectively).