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

SIMPLE SUMMARY: Serum metabolite profiles were compared in healthy participants and lung cancer individuals in two independent screening studies. A reduced level of lipids, particularly cholesteryl esters, was observed in cancer patients. Despite several compounds showing significant differences bet...

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Autores principales: Widłak, Piotr, Jelonek, Karol, Kurczyk, Agata, Żyła, Joanna, Sitkiewicz, Magdalena, Bottoni, Edoardo, Veronesi, Giulia, Polańska, Joanna, Rzyman, Witold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198431/
https://www.ncbi.nlm.nih.gov/pubmed/34072693
http://dx.doi.org/10.3390/cancers13112714
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author Widłak, Piotr
Jelonek, Karol
Kurczyk, Agata
Żyła, Joanna
Sitkiewicz, Magdalena
Bottoni, Edoardo
Veronesi, Giulia
Polańska, Joanna
Rzyman, Witold
author_facet Widłak, Piotr
Jelonek, Karol
Kurczyk, Agata
Żyła, Joanna
Sitkiewicz, Magdalena
Bottoni, Edoardo
Veronesi, Giulia
Polańska, Joanna
Rzyman, Witold
author_sort Widłak, Piotr
collection PubMed
description SIMPLE SUMMARY: Serum metabolite profiles were compared in healthy participants and lung cancer individuals in two independent screening studies. A reduced level of lipids, particularly cholesteryl esters, was observed in cancer patients. Despite several compounds showing significant differences between cancer patients and healthy controls within each study, only a few cancer-related features were common when both studies were compared, including reduced levels of LPC(18:0). A large heterogeneity of serum metabolomes was observed, both within and between studies, which impaired the accuracy of classifiers based on specific metabolites. ABSTRACT: 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.
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spelling pubmed-81984312021-06-14 Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts Widłak, Piotr Jelonek, Karol Kurczyk, Agata Żyła, Joanna Sitkiewicz, Magdalena Bottoni, Edoardo Veronesi, Giulia Polańska, Joanna Rzyman, Witold Cancers (Basel) Article SIMPLE SUMMARY: Serum metabolite profiles were compared in healthy participants and lung cancer individuals in two independent screening studies. A reduced level of lipids, particularly cholesteryl esters, was observed in cancer patients. Despite several compounds showing significant differences between cancer patients and healthy controls within each study, only a few cancer-related features were common when both studies were compared, including reduced levels of LPC(18:0). A large heterogeneity of serum metabolomes was observed, both within and between studies, which impaired the accuracy of classifiers based on specific metabolites. ABSTRACT: 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. MDPI 2021-05-31 /pmc/articles/PMC8198431/ /pubmed/34072693 http://dx.doi.org/10.3390/cancers13112714 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Widłak, Piotr
Jelonek, Karol
Kurczyk, Agata
Żyła, Joanna
Sitkiewicz, Magdalena
Bottoni, Edoardo
Veronesi, Giulia
Polańska, Joanna
Rzyman, Witold
Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts
title Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts
title_full Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts
title_fullStr Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts
title_full_unstemmed Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts
title_short Serum Metabolite Profiles in Participants of Lung Cancer Screening Study; Comparison of Two Independent Cohorts
title_sort serum metabolite profiles in participants of lung cancer screening study; comparison of two independent cohorts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198431/
https://www.ncbi.nlm.nih.gov/pubmed/34072693
http://dx.doi.org/10.3390/cancers13112714
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