An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry
Abstract N-glycosylation is an abundant post-translational modification of most cell-surface proteins. N-glycans play a crucial role in cellular functions like protein folding, protein localization, cell–cell signaling, and immune detection. As different tissue types display different N-glycan profi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50957-w |
| _version_ | 1797363392009207808 |
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| author | Elizabeth N. Wallace Connor A. West Colin T. McDowell Xiaowei Lu Evelyn Bruner Anand S. Mehta Kiyoko F. Aoki-Kinoshita Peggi M. Angel Richard R. Drake |
| author_facet | Elizabeth N. Wallace Connor A. West Colin T. McDowell Xiaowei Lu Evelyn Bruner Anand S. Mehta Kiyoko F. Aoki-Kinoshita Peggi M. Angel Richard R. Drake |
| author_sort | Elizabeth N. Wallace |
| collection | DOAJ |
| description | Abstract N-glycosylation is an abundant post-translational modification of most cell-surface proteins. N-glycans play a crucial role in cellular functions like protein folding, protein localization, cell–cell signaling, and immune detection. As different tissue types display different N-glycan profiles, changes in N-glycan compositions occur in tissue-specific ways with development of disease, like cancer. However, no comparative atlas resource exists for documenting N-glycome alterations across various human tissue types, particularly comparing normal and cancerous tissues. In order to study a broad range of human tissue N-glycomes, N-glycan targeted MALDI imaging mass spectrometry was applied to custom formalin-fixed paraffin-embedded tissue microarrays. These encompassed fifteen human tissue types including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, and uterus. Each array contained both normal and tumor cores from the same pathology block, selected by a pathologist, allowing more in-depth comparisons of the N-glycome differences between tumor and normal and across tissue types. Using established MALDI-IMS workflows and existing N-glycan databases, the N-glycans present in each tissue core were spatially profiled and peak intensity data compiled for comparative analyses. Further structural information was determined for core fucosylation using endoglycosidase F3, and differentiation of sialic acid linkages through stabilization chemistry. Glycan structural differences across the tissue types were compared for oligomannose levels, branching complexity, presence of bisecting N-acetylglucosamine, fucosylation, and sialylation. Collectively, our research identified the N-glycans that were significantly increased and/or decreased in relative abundance in cancer for each tissue type. This study offers valuable information on a wide scale for both normal and cancerous tissues, serving as a reference for future studies and potential diagnostic applications of MALDI-IMS. |
| first_indexed | 2024-03-08T16:20:43Z |
| format | Article |
| id | doaj.art-b99fe5bd597d4068ad3081f8fb25956f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:20:43Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b99fe5bd597d4068ad3081f8fb25956f2024-01-07T12:25:06ZengNature PortfolioScientific Reports2045-23222024-01-0114111510.1038/s41598-023-50957-wAn N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometryElizabeth N. Wallace0Connor A. West1Colin T. McDowell2Xiaowei Lu3Evelyn Bruner4Anand S. Mehta5Kiyoko F. Aoki-Kinoshita6Peggi M. Angel7Richard R. Drake8Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaDepartment of Pathology and Laboratory Medicine, Medical University of South CarolinaDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaDepartment of Bioinformatics, Soka UniversityDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South CarolinaAbstract N-glycosylation is an abundant post-translational modification of most cell-surface proteins. N-glycans play a crucial role in cellular functions like protein folding, protein localization, cell–cell signaling, and immune detection. As different tissue types display different N-glycan profiles, changes in N-glycan compositions occur in tissue-specific ways with development of disease, like cancer. However, no comparative atlas resource exists for documenting N-glycome alterations across various human tissue types, particularly comparing normal and cancerous tissues. In order to study a broad range of human tissue N-glycomes, N-glycan targeted MALDI imaging mass spectrometry was applied to custom formalin-fixed paraffin-embedded tissue microarrays. These encompassed fifteen human tissue types including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, and uterus. Each array contained both normal and tumor cores from the same pathology block, selected by a pathologist, allowing more in-depth comparisons of the N-glycome differences between tumor and normal and across tissue types. Using established MALDI-IMS workflows and existing N-glycan databases, the N-glycans present in each tissue core were spatially profiled and peak intensity data compiled for comparative analyses. Further structural information was determined for core fucosylation using endoglycosidase F3, and differentiation of sialic acid linkages through stabilization chemistry. Glycan structural differences across the tissue types were compared for oligomannose levels, branching complexity, presence of bisecting N-acetylglucosamine, fucosylation, and sialylation. Collectively, our research identified the N-glycans that were significantly increased and/or decreased in relative abundance in cancer for each tissue type. This study offers valuable information on a wide scale for both normal and cancerous tissues, serving as a reference for future studies and potential diagnostic applications of MALDI-IMS.https://doi.org/10.1038/s41598-023-50957-w |
| spellingShingle | Elizabeth N. Wallace Connor A. West Colin T. McDowell Xiaowei Lu Evelyn Bruner Anand S. Mehta Kiyoko F. Aoki-Kinoshita Peggi M. Angel Richard R. Drake An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry Scientific Reports |
| title | An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry |
| title_full | An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry |
| title_fullStr | An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry |
| title_full_unstemmed | An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry |
| title_short | An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry |
| title_sort | n glycome tissue atlas of 15 human normal and cancer tissue types determined by maldi imaging mass spectrometry |
| url | https://doi.org/10.1038/s41598-023-50957-w |
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