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Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis

Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy. Methods: Herein, we identified key genes relevant to CRC metabolism through a comp...

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Autores principales: Zhang, Enkui, Zhou, Xueliang, Fan, Xiaodong, Li, Shuchun, Ding, Chengsheng, Hong, Hiju, Aikemu, Batuer, Yang, Guang, Yesseyeva, Galiya, Yang, Xiao, Ma, Junjun, Zheng, Minhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484590/
https://www.ncbi.nlm.nih.gov/pubmed/37691826
http://dx.doi.org/10.3389/fcell.2023.1173803
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author Zhang, Enkui
Zhou, Xueliang
Fan, Xiaodong
Li, Shuchun
Ding, Chengsheng
Hong, Hiju
Aikemu, Batuer
Yang, Guang
Yesseyeva, Galiya
Yang, Xiao
Ma, Junjun
Zheng, Minhua
author_facet Zhang, Enkui
Zhou, Xueliang
Fan, Xiaodong
Li, Shuchun
Ding, Chengsheng
Hong, Hiju
Aikemu, Batuer
Yang, Guang
Yesseyeva, Galiya
Yang, Xiao
Ma, Junjun
Zheng, Minhua
author_sort Zhang, Enkui
collection PubMed
description Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy. Methods: Herein, we identified key genes relevant to CRC metabolism through a comprehensive analysis of lactate metabolism-related genes from GSEA MsigDB, employing univariate Cox regression analysis and random forest algorithms. Clinical prognostic analysis was performed following identification of three key genes, and consistent clustering enabled the classification of public datasets into three patterns with significant prognostic differences. The molecular pathways and tumor microenvironment (TME) of these patterns were then investigated through correlation analyses. Quantitative PCR was employed to quantify the mRNA expression levels of the three pivotal genes in CRC tissue. Single-cell RNA sequencing data and fluorescent multiplex immunohistochemistry were utilized to analyze relevant T cells and validate the correlation between key genes and CD4(+) T cells. Results: Our analysis revealed that MPC1, COQ2, and ADAMTS13 significantly stratify the cohort into three patterns with distinct prognoses. Additionally, the immune infiltration and molecular pathways were significantly different for each pattern. Among the key genes, MPC1 and COQ2 were positively associated with good prognosis, whereas ADAMTS13 was negatively associated with good prognosis. Single-cell RNA sequencing (scRNA-seq) data illustrated that the relationship between three key genes and T cells, which was further confirmed by the results of fluorescent multiplex immunohistochemistry demonstrating a positive correlation between MPC1 and COQ2 with CD4(+) T cells and a negative correlation between ADAMTS13 and CD4(+) T cells. Discussion: These findings suggest that the three key lactate metabolism genes, MPC1, COQ2, and ADAMTS13, may serve as effective prognostic biomarkers and support the link between lactate metabolism and the immune microenvironment in CRC.
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spelling pubmed-104845902023-09-08 Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis Zhang, Enkui Zhou, Xueliang Fan, Xiaodong Li, Shuchun Ding, Chengsheng Hong, Hiju Aikemu, Batuer Yang, Guang Yesseyeva, Galiya Yang, Xiao Ma, Junjun Zheng, Minhua Front Cell Dev Biol Cell and Developmental Biology Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy. Methods: Herein, we identified key genes relevant to CRC metabolism through a comprehensive analysis of lactate metabolism-related genes from GSEA MsigDB, employing univariate Cox regression analysis and random forest algorithms. Clinical prognostic analysis was performed following identification of three key genes, and consistent clustering enabled the classification of public datasets into three patterns with significant prognostic differences. The molecular pathways and tumor microenvironment (TME) of these patterns were then investigated through correlation analyses. Quantitative PCR was employed to quantify the mRNA expression levels of the three pivotal genes in CRC tissue. Single-cell RNA sequencing data and fluorescent multiplex immunohistochemistry were utilized to analyze relevant T cells and validate the correlation between key genes and CD4(+) T cells. Results: Our analysis revealed that MPC1, COQ2, and ADAMTS13 significantly stratify the cohort into three patterns with distinct prognoses. Additionally, the immune infiltration and molecular pathways were significantly different for each pattern. Among the key genes, MPC1 and COQ2 were positively associated with good prognosis, whereas ADAMTS13 was negatively associated with good prognosis. Single-cell RNA sequencing (scRNA-seq) data illustrated that the relationship between three key genes and T cells, which was further confirmed by the results of fluorescent multiplex immunohistochemistry demonstrating a positive correlation between MPC1 and COQ2 with CD4(+) T cells and a negative correlation between ADAMTS13 and CD4(+) T cells. Discussion: These findings suggest that the three key lactate metabolism genes, MPC1, COQ2, and ADAMTS13, may serve as effective prognostic biomarkers and support the link between lactate metabolism and the immune microenvironment in CRC. Frontiers Media S.A. 2023-08-24 /pmc/articles/PMC10484590/ /pubmed/37691826 http://dx.doi.org/10.3389/fcell.2023.1173803 Text en Copyright © 2023 Zhang, Zhou, Fan, Li, Ding, Hong, Aikemu, Yang, Yesseyeva, Yang, Ma and Zheng. 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 Cell and Developmental Biology
Zhang, Enkui
Zhou, Xueliang
Fan, Xiaodong
Li, Shuchun
Ding, Chengsheng
Hong, Hiju
Aikemu, Batuer
Yang, Guang
Yesseyeva, Galiya
Yang, Xiao
Ma, Junjun
Zheng, Minhua
Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
title Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
title_full Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
title_fullStr Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
title_full_unstemmed Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
title_short Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
title_sort exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484590/
https://www.ncbi.nlm.nih.gov/pubmed/37691826
http://dx.doi.org/10.3389/fcell.2023.1173803
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