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Keywords = Comprehensive Serum Glycopeptide Spectra Analysis

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19 pages, 2925 KiB  
Article
Comprehensive Serum Glycopeptide Spectra Analysis Combined with Machine Learning for Early Detection of Lung Cancer: A Case–Control Study
by Koji Yamazaki, Shigeto Kawauchi, Masaki Okamoto, Kazuhiro Tanabe, Chihiro Hayashi, Mikio Mikami and Tetsuya Kusumoto
Cancers 2025, 17(9), 1474; https://doi.org/10.3390/cancers17091474 - 27 Apr 2025
Cited by 2 | Viewed by 632
Abstract
Background: Lung cancer is among the most prevalent and fatal cancers worldwide. Traditional diagnostic methods, such as computed tomography, are not ideal for screening due to their high cost and radiation exposure. In contrast, blood-based diagnostics, as non-invasive approaches, are expected to reduce [...] Read more.
Background: Lung cancer is among the most prevalent and fatal cancers worldwide. Traditional diagnostic methods, such as computed tomography, are not ideal for screening due to their high cost and radiation exposure. In contrast, blood-based diagnostics, as non-invasive approaches, are expected to reduce patient burden, thereby increasing screening participation and ultimately improving survival rates. However, conventional tumor markers have shown limited effectiveness in early detection. Methods: We recruited 199 patients with lung cancer and 590 healthy volunteers. Nine tumor markers (CEA, CA19-9, CYFRA, AFP, PSA, CA125, CA15-3, SCC antigen, and NCC-ST439) were analyzed, along with enriched glycopeptides (EGPs) derived from serum proteins using liquid chromatography–mass spectrometry. Machine learning models, including decision trees and deep learning approaches, were employed to develop a predictive model for accurately distinguishing lung cancer from healthy controls based on tumor markers and EGP profiles. Results: We found that α1-antitrypsin with fully sialylated biantennary glycan, attached to asparagine 271 (AT271-FSG), and α2-macroglobulin with fully sialylated biantennary glycan, attached to asparagine 70 (MG70-FSG), could significantly distinguish between patients with lung cancer and healthy individuals. Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA), integrating nine conventional tumor markers and 1688 EGPs using a machine learning model, enhanced diagnostic accuracy and achieved an ROC-AUC score of 0.935. It also identified stage I cases with an ROC-AUC of 0.914, indicating the possibility of early-stage detection. The PPV reached 2.8%, which was sufficient for practical application. Conclusions: This method represents a significant advancement in cancer diagnostics, combining multiple biomarkers with cutting-edge machine learning to improve the early detection of lung cancer. Full article
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14 pages, 4110 KiB  
Article
Comprehensive Serum Glycopeptide Spectra Analysis Combined with Artificial Intelligence (CSGSA-AI) to Diagnose Early-Stage Ovarian Cancer
by Kazuhiro Tanabe, Masae Ikeda, Masaru Hayashi, Koji Matsuo, Miwa Yasaka, Hiroko Machida, Masako Shida, Tomoko Katahira, Tadashi Imanishi, Takeshi Hirasawa, Kenji Sato, Hiroshi Yoshida and Mikio Mikami
Cancers 2020, 12(9), 2373; https://doi.org/10.3390/cancers12092373 - 21 Aug 2020
Cited by 26 | Viewed by 4276
Abstract
Ovarian cancer is a leading cause of deaths among gynecological cancers, and a method to detect early-stage epithelial ovarian cancer (EOC) is urgently needed. We aimed to develop an artificial intelligence (AI)-based comprehensive serum glycopeptide spectra analysis (CSGSA-AI) method in combination with convolutional [...] Read more.
Ovarian cancer is a leading cause of deaths among gynecological cancers, and a method to detect early-stage epithelial ovarian cancer (EOC) is urgently needed. We aimed to develop an artificial intelligence (AI)-based comprehensive serum glycopeptide spectra analysis (CSGSA-AI) method in combination with convolutional neural network (CNN) to detect aberrant glycans in serum samples of patients with EOC. We converted serum glycopeptide expression patterns into two-dimensional (2D) barcodes to let CNN learn and distinguish between EOC and non-EOC. CNN was trained using 60% samples and validated using 40% samples. We observed that principal component analysis-based alignment of glycopeptides to generate 2D barcodes significantly increased the diagnostic accuracy (88%) of the method. When CNN was trained with 2D barcodes colored on the basis of serum levels of CA125 and HE4, a diagnostic accuracy of 95% was achieved. We believe that this simple and low-cost method will increase the detection of EOC. Full article
(This article belongs to the Special Issue Non-Invasive Early Detection of Cancers)
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7 pages, 906 KiB  
Brief Report
Utility of Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA) for the Detection of Early Stage Epithelial Ovarian Cancer
by Koji Matsuo, Kazuhiro Tanabe, Masaru Hayashi, Masae Ikeda, Miwa Yasaka, Hiroko Machida, Masako Shida, Kenji Sato, Hiroshi Yoshida, Takeshi Hirasawa, Tadashi Imanishi and Mikio Mikami
Cancers 2020, 12(9), 2374; https://doi.org/10.3390/cancers12092374 - 21 Aug 2020
Cited by 8 | Viewed by 2507
Abstract
Comprehensive serum glycopeptide spectra analysis (CSGSA) evaluates >10,000 serum glycopeptides and identifies unique glycopeptide peaks and patterns via supervised orthogonal partial least-squares discriminant modeling. CSGSA was more accurate than cancer antigen 125 (CA125) or human epididymis protein 4 (HE4) for detecting early stage [...] Read more.
Comprehensive serum glycopeptide spectra analysis (CSGSA) evaluates >10,000 serum glycopeptides and identifies unique glycopeptide peaks and patterns via supervised orthogonal partial least-squares discriminant modeling. CSGSA was more accurate than cancer antigen 125 (CA125) or human epididymis protein 4 (HE4) for detecting early stage epithelial ovarian cancer. Combined CSGSA, CA125, and HE4 had improved diagnostic performance. Thus, CSGSA may be a useful screening tool for detecting early stage epithelial ovarian cancer. Full article
(This article belongs to the Special Issue Targeted Therapy for Ovarian Cancer)
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13 pages, 1983 KiB  
Article
Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA): A Potential New Tool for Early Detection of Ovarian Cancer
by Masaru Hayashi, Koji Matsuo, Kazuhiro Tanabe, Masae Ikeda, Mariko Miyazawa, Miwa Yasaka, Hiroko Machida, Masako Shida, Tadashi Imanishi, Brendan H. Grubbs, Takeshi Hirasawa and Mikio Mikami
Cancers 2019, 11(5), 591; https://doi.org/10.3390/cancers11050591 - 27 Apr 2019
Cited by 15 | Viewed by 3622
Abstract
Objectives: To conduct a comprehensive glycopeptide spectra analysis of serum between cancer and non-cancer patients to identify early biomarkers of epithelial ovarian cancer (EOC). Methods: Approximately 30,000 glycopeptide peaks were detected from the digested serum glycoproteins of 39 EOC patients (23 early-stage, 16 [...] Read more.
Objectives: To conduct a comprehensive glycopeptide spectra analysis of serum between cancer and non-cancer patients to identify early biomarkers of epithelial ovarian cancer (EOC). Methods: Approximately 30,000 glycopeptide peaks were detected from the digested serum glycoproteins of 39 EOC patients (23 early-stage, 16 advanced-stage) and 45 non-cancer patients (27 leiomyoma and ovarian cyst cases, 18 endometrioma cases) by liquid chromatography mass spectrometry (LC–MS). The differential glycopeptide peak spectra were analyzed to distinguish between cancer and non-cancer groups by employing multivariate analysis including principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and heat maps. Results: Examined spectral peaks were filtered down to 2281 serum quantitative glycopeptide signatures for differentiation between ovarian cancer and controls using multivariate analysis. The OPLS-DA model using cross-validation parameters R2 and Q2 and score plots of the serum samples significantly differentiated the EOC group from the non-cancer control group. In addition, women with early-stage clear cell carcinoma and endometriomas were clearly distinguished from each other by OPLS-DA as well as by PCA and heat maps. Conclusions: Our study demonstrates the potential of comprehensive serum glycoprotein analysis as a useful tool for ovarian cancer detection. Full article
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