<i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)

It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients...

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Main Authors: Masanori Oshi, Danya Ziazadeh, Rongrong Wu, Kohei Chida, Akimitsu Yamada, Shinya Yamamoto, Kazutaka Narui, Li Yan, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/15/13/3489
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author Masanori Oshi
Danya Ziazadeh
Rongrong Wu
Kohei Chida
Akimitsu Yamada
Shinya Yamamoto
Kazutaka Narui
Li Yan
Takashi Ishikawa
Itaru Endo
Kazuaki Takabe
author_facet Masanori Oshi
Danya Ziazadeh
Rongrong Wu
Kohei Chida
Akimitsu Yamada
Shinya Yamamoto
Kazutaka Narui
Li Yan
Takashi Ishikawa
Itaru Endo
Kazuaki Takabe
author_sort Masanori Oshi
collection DOAJ
description It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of <i>GALNT1</i> expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of <i>GALNT1</i> expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest <i>GALNT1</i> expression compared to ER-positive/HER2-negative BC, <i>GALNT1</i> levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-<i>GALNT1</i> expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in <i>GALNT1</i> expression levels among AYAs and older patients. However, high <i>GALNT1</i> expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high <i>GALNT1</i> expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high <i>GALNT1</i> expression demonstrated low levels of CD8<sup>+</sup> T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of <i>GALNT1</i> BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that <i>GALNT1</i> expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients.
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spelling doaj.art-b73e74cc693f415a970f2af009a9ca262023-11-18T16:17:44ZengMDPI AGCancers2072-66942023-07-011513348910.3390/cancers15133489<i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)Masanori Oshi0Danya Ziazadeh1Rongrong Wu2Kohei Chida3Akimitsu Yamada4Shinya Yamamoto5Kazutaka Narui6Li Yan7Takashi Ishikawa8Itaru Endo9Kazuaki Takabe10Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, JapanDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama 232-0024, JapanDepartment of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama 232-0024, JapanDepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, JapanDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAIt is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of <i>GALNT1</i> expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of <i>GALNT1</i> expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest <i>GALNT1</i> expression compared to ER-positive/HER2-negative BC, <i>GALNT1</i> levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-<i>GALNT1</i> expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in <i>GALNT1</i> expression levels among AYAs and older patients. However, high <i>GALNT1</i> expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high <i>GALNT1</i> expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high <i>GALNT1</i> expression demonstrated low levels of CD8<sup>+</sup> T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of <i>GALNT1</i> BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that <i>GALNT1</i> expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients.https://www.mdpi.com/2072-6694/15/13/3489angiogenesisAYAbreast cancer<i>GALNT1</i>gene expressionsignaling
spellingShingle Masanori Oshi
Danya Ziazadeh
Rongrong Wu
Kohei Chida
Akimitsu Yamada
Shinya Yamamoto
Kazutaka Narui
Li Yan
Takashi Ishikawa
Itaru Endo
Kazuaki Takabe
<i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)
Cancers
angiogenesis
AYA
breast cancer
<i>GALNT1</i>
gene expression
signaling
title <i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)
title_full <i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)
title_fullStr <i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)
title_full_unstemmed <i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)
title_short <i>GALNT1</i> Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)
title_sort i galnt1 i expression is associated with angiogenesis and is a prognostic biomarker for breast cancer in adolescents and young adults aya
topic angiogenesis
AYA
breast cancer
<i>GALNT1</i>
gene expression
signaling
url https://www.mdpi.com/2072-6694/15/13/3489
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