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Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study
The interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study examines the link between tumor metabolome and prognosis by sex for CRC patients. Using untargeted...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875032/ https://www.ncbi.nlm.nih.gov/pubmed/35208238 http://dx.doi.org/10.3390/metabo12020164 |
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author | Shen, Xinyi Cai, Yuping Lu, Lingeng Huang, Huang Yan, Hong Paty, Philip B. Muca, Engjel Ahuja, Nita Zhang, Yawei Johnson, Caroline H. Khan, Sajid A. |
author_facet | Shen, Xinyi Cai, Yuping Lu, Lingeng Huang, Huang Yan, Hong Paty, Philip B. Muca, Engjel Ahuja, Nita Zhang, Yawei Johnson, Caroline H. Khan, Sajid A. |
author_sort | Shen, Xinyi |
collection | PubMed |
description | The interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study examines the link between tumor metabolome and prognosis by sex for CRC patients. Using untargeted metabolomics analysis, abundances of 91 metabolites were obtained from primary tumor tissues from 197 patients (N = 95 females, N = 102 males) after surgical colectomy for stage I-III CRC. Cox Proportional hazard (PH) regression models estimated the associations between tumor metabolome and 5-year overall survival (OS) and recurrence-free survival (RFS), and their interactions with sex. Eleven metabolites had significant sex differences in their associations with 5-year OS, and five metabolites for 5-year RFS. The metabolites asparagine and serine had sex interactions for both OS and RFS. Furthermore, in the asparagine synthetase (ASNS)-catalyzed asparagine synthesis pathway, asparagine was associated with substantially poorer OS (HR (95% CI): 6.39 (1.78–22.91)) and RFS (HR (95% CI): 4.36 (1.39–13.68)) for female patients only. Similar prognostic disadvantages in females were seen in lysophospholipid and polyamine synthesis. Unique metabolite profiles indicated that increased asparagine synthesis was associated with poorer prognosis for females only, providing insight into precision medicine for CRC treatment stratified by sex. |
format | Online Article Text |
id | pubmed-8875032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88750322022-02-26 Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study Shen, Xinyi Cai, Yuping Lu, Lingeng Huang, Huang Yan, Hong Paty, Philip B. Muca, Engjel Ahuja, Nita Zhang, Yawei Johnson, Caroline H. Khan, Sajid A. Metabolites Article The interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study examines the link between tumor metabolome and prognosis by sex for CRC patients. Using untargeted metabolomics analysis, abundances of 91 metabolites were obtained from primary tumor tissues from 197 patients (N = 95 females, N = 102 males) after surgical colectomy for stage I-III CRC. Cox Proportional hazard (PH) regression models estimated the associations between tumor metabolome and 5-year overall survival (OS) and recurrence-free survival (RFS), and their interactions with sex. Eleven metabolites had significant sex differences in their associations with 5-year OS, and five metabolites for 5-year RFS. The metabolites asparagine and serine had sex interactions for both OS and RFS. Furthermore, in the asparagine synthetase (ASNS)-catalyzed asparagine synthesis pathway, asparagine was associated with substantially poorer OS (HR (95% CI): 6.39 (1.78–22.91)) and RFS (HR (95% CI): 4.36 (1.39–13.68)) for female patients only. Similar prognostic disadvantages in females were seen in lysophospholipid and polyamine synthesis. Unique metabolite profiles indicated that increased asparagine synthesis was associated with poorer prognosis for females only, providing insight into precision medicine for CRC treatment stratified by sex. MDPI 2022-02-09 /pmc/articles/PMC8875032/ /pubmed/35208238 http://dx.doi.org/10.3390/metabo12020164 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shen, Xinyi Cai, Yuping Lu, Lingeng Huang, Huang Yan, Hong Paty, Philip B. Muca, Engjel Ahuja, Nita Zhang, Yawei Johnson, Caroline H. Khan, Sajid A. Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study |
title | Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study |
title_full | Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study |
title_fullStr | Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study |
title_full_unstemmed | Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study |
title_short | Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study |
title_sort | asparagine metabolism in tumors is linked to poor survival in females with colorectal cancer: a cohort study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875032/ https://www.ncbi.nlm.nih.gov/pubmed/35208238 http://dx.doi.org/10.3390/metabo12020164 |
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