Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors
Abstract Serum biomarker monitoring is essential for management of germ‐cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N‐glycan‐based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensi...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1035 |
| _version_ | 1828179412031373312 |
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| author | Takuma Narita Shingo Hatakeyama Tohru Yoneyama Shintaro Narita Shinichi Yamashita Koji Mitsuzuka Toshihiko Sakurai Sadafumi Kawamura Tatsuo Tochigi Ippei Takahashi Shigeyuki Nakaji Yuki Tobisawa Hayato Yamamoto Takuya Koie Norihiko Tsuchiya Tomonori Habuchi Yoichi Arai Chikara Ohyama |
| author_facet | Takuma Narita Shingo Hatakeyama Tohru Yoneyama Shintaro Narita Shinichi Yamashita Koji Mitsuzuka Toshihiko Sakurai Sadafumi Kawamura Tatsuo Tochigi Ippei Takahashi Shigeyuki Nakaji Yuki Tobisawa Hayato Yamamoto Takuya Koie Norihiko Tsuchiya Tomonori Habuchi Yoichi Arai Chikara Ohyama |
| author_sort | Takuma Narita |
| collection | DOAJ |
| description | Abstract Serum biomarker monitoring is essential for management of germ‐cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N‐glycan‐based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensive N‐glycan structural analysis of sera from 54 untreated GCT patients and 103 age‐adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N‐glycans were selected from those with the highest association; cutoff concentration values were established, and an N‐glycan score was created based on the number of positive N‐glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N‐glycans significantly associated with GCT patients. The accuracy of the N‐glycan score for GCT was significant with an area‐under‐the‐curve (AUC) value of 0.87. Diagnostically, the N‐glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N‐glycan score comprised four candidate N‐glycans. The predictive value of the prognostic N‐glycan score was significant, with an AUC value of 0.89. A high value prognostic N‐glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N‐glycan analysis and compared to whole sera. Candidate N‐glycans in Ig‐fractions were significantly decreased; therefore, the carrier protein for candidate N‐glycans is likely not an immunoglobulin. In summary, our newly developed N‐glycan score seems to be a practical diagnostic and prognostic method for GCT. |
| first_indexed | 2024-04-12T05:28:53Z |
| format | Article |
| id | doaj.art-685e44249ed44e67b41894c599575e03 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-12T05:28:53Z |
| publishDate | 2017-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-685e44249ed44e67b41894c599575e032022-12-22T03:46:10ZengWileyCancer Medicine2045-76342017-04-016473974810.1002/cam4.1035Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumorsTakuma Narita0Shingo Hatakeyama1Tohru Yoneyama2Shintaro Narita3Shinichi Yamashita4Koji Mitsuzuka5Toshihiko Sakurai6Sadafumi Kawamura7Tatsuo Tochigi8Ippei Takahashi9Shigeyuki Nakaji10Yuki Tobisawa11Hayato Yamamoto12Takuya Koie13Norihiko Tsuchiya14Tomonori Habuchi15Yoichi Arai16Chikara Ohyama17Department of Urology Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Urology Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Advanced Transplant and Regenerative Medicine Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Urology Akita University Graduate School of Medicine Akita JapanDepartment of Urology Tohoku University Graduate School of Medicine Sendai JapanDepartment of Urology Tohoku University Graduate School of Medicine Sendai JapanDepartment of Urology Yamagata University Graduate School of Medicine Yamagata JapanDepartment of Urology Miyagi Cancer Center Natori JapanDepartment of Urology Miyagi Cancer Center Natori JapanDepartment of Social Medicine Hirosaki University School of Medicine Hirosaki JapanDepartment of Social Medicine Hirosaki University School of Medicine Hirosaki JapanDepartment of Urology Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Urology Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Urology Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Urology Yamagata University Graduate School of Medicine Yamagata JapanDepartment of Urology Akita University Graduate School of Medicine Akita JapanDepartment of Urology Tohoku University Graduate School of Medicine Sendai JapanDepartment of Urology Hirosaki University Graduate School of Medicine Hirosaki JapanAbstract Serum biomarker monitoring is essential for management of germ‐cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N‐glycan‐based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensive N‐glycan structural analysis of sera from 54 untreated GCT patients and 103 age‐adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N‐glycans were selected from those with the highest association; cutoff concentration values were established, and an N‐glycan score was created based on the number of positive N‐glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N‐glycans significantly associated with GCT patients. The accuracy of the N‐glycan score for GCT was significant with an area‐under‐the‐curve (AUC) value of 0.87. Diagnostically, the N‐glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N‐glycan score comprised four candidate N‐glycans. The predictive value of the prognostic N‐glycan score was significant, with an AUC value of 0.89. A high value prognostic N‐glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N‐glycan analysis and compared to whole sera. Candidate N‐glycans in Ig‐fractions were significantly decreased; therefore, the carrier protein for candidate N‐glycans is likely not an immunoglobulin. In summary, our newly developed N‐glycan score seems to be a practical diagnostic and prognostic method for GCT.https://doi.org/10.1002/cam4.1035Biomarkergerm‐cell tumorsglycoblottingmass spectrometryserum N‐glycan |
| spellingShingle | Takuma Narita Shingo Hatakeyama Tohru Yoneyama Shintaro Narita Shinichi Yamashita Koji Mitsuzuka Toshihiko Sakurai Sadafumi Kawamura Tatsuo Tochigi Ippei Takahashi Shigeyuki Nakaji Yuki Tobisawa Hayato Yamamoto Takuya Koie Norihiko Tsuchiya Tomonori Habuchi Yoichi Arai Chikara Ohyama Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors Cancer Medicine Biomarker germ‐cell tumors glycoblotting mass spectrometry serum N‐glycan |
| title | Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors |
| title_full | Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors |
| title_fullStr | Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors |
| title_full_unstemmed | Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors |
| title_short | Clinical implications of serum N‐glycan profiling as a diagnostic and prognostic biomarker in germ‐cell tumors |
| title_sort | clinical implications of serum n glycan profiling as a diagnostic and prognostic biomarker in germ cell tumors |
| topic | Biomarker germ‐cell tumors glycoblotting mass spectrometry serum N‐glycan |
| url | https://doi.org/10.1002/cam4.1035 |
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