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Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma

Glutamine metabolism (GM) plays a critical role in hepatocellular carcinoma (HCC); however, a comprehensive methodology to quantify GM activity is still lacking. We developed a transcriptome-based GMScore to evaluate GM activity and investigated the association of GMScore with prognosis and therapeu...

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Autores principales: Ying, Leqian, Cheng, Meilian, Lu, Yi, Tao, Qin, Chen, Xiaofeng, Shen, Bo, Xiong, Fen, Hu, Zhangmin, Wang, Deqiang, Li, Xiaoqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724684/
https://www.ncbi.nlm.nih.gov/pubmed/34992505
http://dx.doi.org/10.3389/pore.2021.1610075
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author Ying, Leqian
Cheng, Meilian
Lu, Yi
Tao, Qin
Chen, Xiaofeng
Shen, Bo
Xiong, Fen
Hu, Zhangmin
Wang, Deqiang
Li, Xiaoqin
author_facet Ying, Leqian
Cheng, Meilian
Lu, Yi
Tao, Qin
Chen, Xiaofeng
Shen, Bo
Xiong, Fen
Hu, Zhangmin
Wang, Deqiang
Li, Xiaoqin
author_sort Ying, Leqian
collection PubMed
description Glutamine metabolism (GM) plays a critical role in hepatocellular carcinoma (HCC); however, a comprehensive methodology to quantify GM activity is still lacking. We developed a transcriptome-based GMScore to evaluate GM activity and investigated the association of GMScore with prognosis and therapeutic resistance. Two independent HCC cohorts with transcriptome data were selected from The Cancer Genome Atlas (TCGA, n = 365) and the International Cancer Genome Consortium (ICGC, n = 231). The expression of 41 GM-associated genes were used to construct and validate GMScore. Several genomic or transcriptomic biomarkers were also estimated. Tumor response to immune checkpoint inhibitors (ICIs) was predicted using the tumor immune dysfunction and exclusion algorithm. GMScore was closely correlated with patient characteristics, including stage, histology grade, alpha-fetoprotein level, and vascular invasion. High GMScore was an independent risk factor for overall survival (OS) in both cohorts (HR = 4.2 and 3.91, both p < 0.001), superior to clinical indices and other biomarkers. High GMScore presented transcriptome features to indicate cell growth advantages and genetic stability, which was associated with poor OS of patients who received transcatheter arterial chemoembolization (TACE). High GMScore was also related to high expression of immune checkpoint genes, increased infiltration of regulatory T cells, and decreased infiltration of M1 macrophages. More importantly, high GMScore indicated poor predicted responses to ICIs, which could be verified in an ICI-treated melanoma cohort. In conclusion, GMScore is a strong prognostic index that may be integrated into existing clinical algorithms. A high GMScore may indicate resistance to TACE and ICIs based on its transcriptome and immune features. Validations using other HCC cohorts, especially ICI-treated HCC cohorts, are necessary.
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spelling pubmed-87246842022-01-05 Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma Ying, Leqian Cheng, Meilian Lu, Yi Tao, Qin Chen, Xiaofeng Shen, Bo Xiong, Fen Hu, Zhangmin Wang, Deqiang Li, Xiaoqin Pathol Oncol Res Pathology and Oncology Archive Glutamine metabolism (GM) plays a critical role in hepatocellular carcinoma (HCC); however, a comprehensive methodology to quantify GM activity is still lacking. We developed a transcriptome-based GMScore to evaluate GM activity and investigated the association of GMScore with prognosis and therapeutic resistance. Two independent HCC cohorts with transcriptome data were selected from The Cancer Genome Atlas (TCGA, n = 365) and the International Cancer Genome Consortium (ICGC, n = 231). The expression of 41 GM-associated genes were used to construct and validate GMScore. Several genomic or transcriptomic biomarkers were also estimated. Tumor response to immune checkpoint inhibitors (ICIs) was predicted using the tumor immune dysfunction and exclusion algorithm. GMScore was closely correlated with patient characteristics, including stage, histology grade, alpha-fetoprotein level, and vascular invasion. High GMScore was an independent risk factor for overall survival (OS) in both cohorts (HR = 4.2 and 3.91, both p < 0.001), superior to clinical indices and other biomarkers. High GMScore presented transcriptome features to indicate cell growth advantages and genetic stability, which was associated with poor OS of patients who received transcatheter arterial chemoembolization (TACE). High GMScore was also related to high expression of immune checkpoint genes, increased infiltration of regulatory T cells, and decreased infiltration of M1 macrophages. More importantly, high GMScore indicated poor predicted responses to ICIs, which could be verified in an ICI-treated melanoma cohort. In conclusion, GMScore is a strong prognostic index that may be integrated into existing clinical algorithms. A high GMScore may indicate resistance to TACE and ICIs based on its transcriptome and immune features. Validations using other HCC cohorts, especially ICI-treated HCC cohorts, are necessary. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8724684/ /pubmed/34992505 http://dx.doi.org/10.3389/pore.2021.1610075 Text en Copyright © 2021 Ying, Cheng, Lu, Tao, Chen, Shen, Xiong, Hu, Wang and Li. 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 Pathology and Oncology Archive
Ying, Leqian
Cheng, Meilian
Lu, Yi
Tao, Qin
Chen, Xiaofeng
Shen, Bo
Xiong, Fen
Hu, Zhangmin
Wang, Deqiang
Li, Xiaoqin
Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma
title Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma
title_full Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma
title_fullStr Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma
title_full_unstemmed Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma
title_short Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma
title_sort glutamine metabolism scoring predicts prognosis and therapeutic resistance in hepatocellular carcinoma
topic Pathology and Oncology Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724684/
https://www.ncbi.nlm.nih.gov/pubmed/34992505
http://dx.doi.org/10.3389/pore.2021.1610075
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