Combination of urinary free-glycan markers for the diagnosis of various malignant tumors
Abstract Many urinary free-glycan markers were identified in our previous studies. Here, the clinical utility of these markers was examined. Urine samples taken from 120 healthy subjects and 503 patients with various malignant tumors were analyzed. Four lactose-core glycans containing N-glycolylgluc...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-94496-y |
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| author | Miki Tanaka-Okamoto Ken Hanzawa Takashi Yamamoto Tomoki Michida Kenji Ikezawa Kazuyoshi Ohkawa Kazumi Nishino Takafumi Yokota Michihide Maeda Ken-ichi Yoshida Satoshi Takenaka Masayuki Ohue Tomoyuki Yamasaki Yasuhide Miyamoto |
| author_facet | Miki Tanaka-Okamoto Ken Hanzawa Takashi Yamamoto Tomoki Michida Kenji Ikezawa Kazuyoshi Ohkawa Kazumi Nishino Takafumi Yokota Michihide Maeda Ken-ichi Yoshida Satoshi Takenaka Masayuki Ohue Tomoyuki Yamasaki Yasuhide Miyamoto |
| author_sort | Miki Tanaka-Okamoto |
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| description | Abstract Many urinary free-glycan markers were identified in our previous studies. Here, the clinical utility of these markers was examined. Urine samples taken from 120 healthy subjects and 503 patients with various malignant tumors were analyzed. Four lactose-core glycans containing N-glycolylglucosamine (GlcNGc) were synthesized and used as internal standards (ISs). Free-glycans were isolated using a two-step column purification procedure, pyridylaminated, and subjected to LC-selected reaction monitoring. Assay validation was performed using four ISs and eight reference glycans. Twelve markers composed of three sialyl lactose-core glycans, three sulfated glycans, four Gn1-core free-N-glycans, and two glycans with unusual structures were selected to investigate their effectiveness for cancer diagnosis. Markers were simultaneously measured and the relative area ratio (marker/IS) quantified. This method was shown to be accurate and precise by repeated analysis of calibrators and quality control samples in urine. Receiver operating characteristic curve analyses revealed that individual markers were not sufficient for highly accurate diagnosis. However, a combination of four markers resulted in higher area under curves of 0.910, 0.867, and 0.914 for gastric, colorectal, and pancreatic cancers, respectively. Moreover, levels of these markers were elevated in various other malignancies. These analyses demonstrated high clinical utility of the free-glycan markers. |
| format | Article |
| id | doaj-art-aa95acf528e9454cac42b204bdba883e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-aa95acf528e9454cac42b204bdba883e2025-08-20T03:40:44ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-94496-yCombination of urinary free-glycan markers for the diagnosis of various malignant tumorsMiki Tanaka-Okamoto0Ken Hanzawa1Takashi Yamamoto2Tomoki Michida3Kenji Ikezawa4Kazuyoshi Ohkawa5Kazumi Nishino6Takafumi Yokota7Michihide Maeda8Ken-ichi Yoshida9Satoshi Takenaka10Masayuki Ohue11Tomoyuki Yamasaki12Yasuhide Miyamoto13Department of Glyco-Oncology and Medical Biochemistry, Osaka International Cancer InstituteGlycoanalytical Chemistry Lab, Institute for Glyco-Core Research (iGCORE), Gifu UniversityDepartment of Clinical Laboratory, Osaka International Cancer InstituteDepartment of Gastrointestinal Oncology, Osaka International Cancer InstituteDepartment of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer InstituteDepartment of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer InstituteDepartment of Thoracic Oncology, Osaka International Cancer InstituteDepartment of Hematology, Osaka International Cancer InstituteDepartment of Gynecology, Osaka International Cancer InstituteDepartment of Diagnostic Pathology and Cytology, Osaka International Cancer InstituteDepartment of Orthopedic Surgery, Osaka International Cancer InstituteDepartment of Gastroenterological Surgery, Osaka International Cancer InstituteDepartment of Clinical Laboratory, Osaka International Cancer InstituteDepartment of Clinical Laboratory, Osaka International Cancer InstituteAbstract Many urinary free-glycan markers were identified in our previous studies. Here, the clinical utility of these markers was examined. Urine samples taken from 120 healthy subjects and 503 patients with various malignant tumors were analyzed. Four lactose-core glycans containing N-glycolylglucosamine (GlcNGc) were synthesized and used as internal standards (ISs). Free-glycans were isolated using a two-step column purification procedure, pyridylaminated, and subjected to LC-selected reaction monitoring. Assay validation was performed using four ISs and eight reference glycans. Twelve markers composed of three sialyl lactose-core glycans, three sulfated glycans, four Gn1-core free-N-glycans, and two glycans with unusual structures were selected to investigate their effectiveness for cancer diagnosis. Markers were simultaneously measured and the relative area ratio (marker/IS) quantified. This method was shown to be accurate and precise by repeated analysis of calibrators and quality control samples in urine. Receiver operating characteristic curve analyses revealed that individual markers were not sufficient for highly accurate diagnosis. However, a combination of four markers resulted in higher area under curves of 0.910, 0.867, and 0.914 for gastric, colorectal, and pancreatic cancers, respectively. Moreover, levels of these markers were elevated in various other malignancies. These analyses demonstrated high clinical utility of the free-glycan markers.https://doi.org/10.1038/s41598-025-94496-yCancerFree-glycanMarkerSRMUrine |
| spellingShingle | Miki Tanaka-Okamoto Ken Hanzawa Takashi Yamamoto Tomoki Michida Kenji Ikezawa Kazuyoshi Ohkawa Kazumi Nishino Takafumi Yokota Michihide Maeda Ken-ichi Yoshida Satoshi Takenaka Masayuki Ohue Tomoyuki Yamasaki Yasuhide Miyamoto Combination of urinary free-glycan markers for the diagnosis of various malignant tumors Scientific Reports Cancer Free-glycan Marker SRM Urine |
| title | Combination of urinary free-glycan markers for the diagnosis of various malignant tumors |
| title_full | Combination of urinary free-glycan markers for the diagnosis of various malignant tumors |
| title_fullStr | Combination of urinary free-glycan markers for the diagnosis of various malignant tumors |
| title_full_unstemmed | Combination of urinary free-glycan markers for the diagnosis of various malignant tumors |
| title_short | Combination of urinary free-glycan markers for the diagnosis of various malignant tumors |
| title_sort | combination of urinary free glycan markers for the diagnosis of various malignant tumors |
| topic | Cancer Free-glycan Marker SRM Urine |
| url | https://doi.org/10.1038/s41598-025-94496-y |
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