Cargando…

Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome

Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advan...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Zhi, Wei, Qingfeng, Wan, Xianghui, Zhong, Xiaoming, Liu, Lijuan, Zeng, Jiquan, Mao, Lihua, Han, Xiaojian, Tou, Fangfang, Rao, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201339/
https://www.ncbi.nlm.nih.gov/pubmed/35720415
http://dx.doi.org/10.3389/fimmu.2022.921317
_version_ 1784728290230009856
author Zheng, Zhi
Wei, Qingfeng
Wan, Xianghui
Zhong, Xiaoming
Liu, Lijuan
Zeng, Jiquan
Mao, Lihua
Han, Xiaojian
Tou, Fangfang
Rao, Jun
author_facet Zheng, Zhi
Wei, Qingfeng
Wan, Xianghui
Zhong, Xiaoming
Liu, Lijuan
Zeng, Jiquan
Mao, Lihua
Han, Xiaojian
Tou, Fangfang
Rao, Jun
author_sort Zheng, Zhi
collection PubMed
description Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment.
format Online
Article
Text
id pubmed-9201339
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92013392022-06-17 Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome Zheng, Zhi Wei, Qingfeng Wan, Xianghui Zhong, Xiaoming Liu, Lijuan Zeng, Jiquan Mao, Lihua Han, Xiaojian Tou, Fangfang Rao, Jun Front Immunol Immunology Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201339/ /pubmed/35720415 http://dx.doi.org/10.3389/fimmu.2022.921317 Text en Copyright © 2022 Zheng, Wei, Wan, Zhong, Liu, Zeng, Mao, Han, Tou and Rao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zheng, Zhi
Wei, Qingfeng
Wan, Xianghui
Zhong, Xiaoming
Liu, Lijuan
Zeng, Jiquan
Mao, Lihua
Han, Xiaojian
Tou, Fangfang
Rao, Jun
Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome
title Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome
title_full Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome
title_fullStr Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome
title_full_unstemmed Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome
title_short Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome
title_sort correlation analysis between trace elements and colorectal cancer metabolism by integrated serum proteome and metabolome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201339/
https://www.ncbi.nlm.nih.gov/pubmed/35720415
http://dx.doi.org/10.3389/fimmu.2022.921317
work_keys_str_mv AT zhengzhi correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT weiqingfeng correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT wanxianghui correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT zhongxiaoming correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT liulijuan correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT zengjiquan correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT maolihua correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT hanxiaojian correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT toufangfang correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome
AT raojun correlationanalysisbetweentraceelementsandcolorectalcancermetabolismbyintegratedserumproteomeandmetabolome