N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis

Abstract Background It is well established that the cancerous transformation of cells is accompanied by profound alterations in glycosylation. In this study, we demonstrate the diagnostic potential of N-glycan profiling in tissue specimens from patients, primarily representing the two major types of...

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Main Authors: Erika Lattova, Jana Skrickova, Jitka Hausnerova, Karolina Krystofova, Zbynek Zdrahal, Leos Kren, Mikulas Popovic
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-025-06904-6
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author Erika Lattova
Jana Skrickova
Jitka Hausnerova
Karolina Krystofova
Zbynek Zdrahal
Leos Kren
Mikulas Popovic
author_facet Erika Lattova
Jana Skrickova
Jitka Hausnerova
Karolina Krystofova
Zbynek Zdrahal
Leos Kren
Mikulas Popovic
author_sort Erika Lattova
collection DOAJ
description Abstract Background It is well established that the cancerous transformation of cells is accompanied by profound alterations in glycosylation. In this study, we demonstrate the diagnostic potential of N-glycan profiling in tissue specimens from patients, primarily representing the two major types of lung cancer: non-small cell and small cell lung cancer. Methods Lung tissues and biopsies obtained from surgery and bronchoscopy underwent sample processing and enzymatic digestion. After labeling, glycans were analyzed employing matrix-assisted laser desorption/ionization mass spectrometry. Statistical analysis was conducted using methods following principles of compositional data analysis. Results Comparison of glycan profiles demonstrated an increase in paucimannose and high mannose glycans in most tumor specimens, including those with inflammation and histological negative for malignancy. Cancerous tissues exhibited more profound changes in glycosylation. Despite the high heterogeneity in profiles, two main groups of not detected glycans in peritumoral tissues, considered as controls, were observed to correlate with cancer progression in patients. One with complex polylactosamine multifucosylated glycans frequently harboring terminal N-acetyl-glucosamine residues. These glycans were present in most tumors, with their numbers and intensities increasing as cancer progressed. In contrast, the second group exhibited polylactosamine glycans sporadically. Instead, the biopsies of several patients with rapid progression displayed a significant presence in a set of tri- and tetra-antennary core fucosylated glycans having mostly unoccupied N-acetyl-glucosamine residues unless carrying additional fucose unit(s). Conclusions The results imply distinct glycosylation patterns even in patients with the same histological type of lung cancer, supporting trends toward personalized diagnosis and more tailored therapies. Currently, tissue biopsies remain the gold standard for diagnosing premalignant and malignant lesions in the lung. Expanded knowledge on glycosylation in these lesions could contribute to improved diagnostic accuracy and better monitoring of malignant disease progression in clinical practice. Graphical abstract
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spelling doaj-art-8b0faa1af2eb40da90596f32db46a35b2025-08-20T04:03:01ZengBMCJournal of Translational Medicine1479-58762025-08-0123111510.1186/s12967-025-06904-6N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosisErika Lattova0Jana Skrickova1Jitka Hausnerova2Karolina Krystofova3Zbynek Zdrahal4Leos Kren5Mikulas Popovic6Central European Institute for Technology, Masaryk UniversityDepartment of Respiratory Diseases and TB, University Hospital Brno and Medical Faculty of Masaryk UniversityDepartment of Pathology, University Hospital and Medical Faculty of Masaryk UniversityCentral European Institute for Technology, Masaryk UniversityCentral European Institute for Technology, Masaryk UniversityDepartment of Pathology, University Hospital and Medical Faculty of Masaryk UniversityThe Institute of Human Virology, University of MarylandAbstract Background It is well established that the cancerous transformation of cells is accompanied by profound alterations in glycosylation. In this study, we demonstrate the diagnostic potential of N-glycan profiling in tissue specimens from patients, primarily representing the two major types of lung cancer: non-small cell and small cell lung cancer. Methods Lung tissues and biopsies obtained from surgery and bronchoscopy underwent sample processing and enzymatic digestion. After labeling, glycans were analyzed employing matrix-assisted laser desorption/ionization mass spectrometry. Statistical analysis was conducted using methods following principles of compositional data analysis. Results Comparison of glycan profiles demonstrated an increase in paucimannose and high mannose glycans in most tumor specimens, including those with inflammation and histological negative for malignancy. Cancerous tissues exhibited more profound changes in glycosylation. Despite the high heterogeneity in profiles, two main groups of not detected glycans in peritumoral tissues, considered as controls, were observed to correlate with cancer progression in patients. One with complex polylactosamine multifucosylated glycans frequently harboring terminal N-acetyl-glucosamine residues. These glycans were present in most tumors, with their numbers and intensities increasing as cancer progressed. In contrast, the second group exhibited polylactosamine glycans sporadically. Instead, the biopsies of several patients with rapid progression displayed a significant presence in a set of tri- and tetra-antennary core fucosylated glycans having mostly unoccupied N-acetyl-glucosamine residues unless carrying additional fucose unit(s). Conclusions The results imply distinct glycosylation patterns even in patients with the same histological type of lung cancer, supporting trends toward personalized diagnosis and more tailored therapies. Currently, tissue biopsies remain the gold standard for diagnosing premalignant and malignant lesions in the lung. Expanded knowledge on glycosylation in these lesions could contribute to improved diagnostic accuracy and better monitoring of malignant disease progression in clinical practice. Graphical abstracthttps://doi.org/10.1186/s12967-025-06904-6Lung cancerGlycosylationN-glycansBranched glycansFucosylationMALDI-MS
spellingShingle Erika Lattova
Jana Skrickova
Jitka Hausnerova
Karolina Krystofova
Zbynek Zdrahal
Leos Kren
Mikulas Popovic
N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis
Journal of Translational Medicine
Lung cancer
Glycosylation
N-glycans
Branched glycans
Fucosylation
MALDI-MS
title N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis
title_full N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis
title_fullStr N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis
title_full_unstemmed N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis
title_short N-glycans in lung tissue specimens: a prospective target for enhanced cancer diagnosis and prognosis
title_sort n glycans in lung tissue specimens a prospective target for enhanced cancer diagnosis and prognosis
topic Lung cancer
Glycosylation
N-glycans
Branched glycans
Fucosylation
MALDI-MS
url https://doi.org/10.1186/s12967-025-06904-6
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