A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) ranks among the most lethal malignancies around the world. However, the current management strategies for predicting prognosis in HCC patients remain unreliable. Our study developed a robust prognostic model based on glutamine metabolism associated-genes (GMAG...

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Main Authors: Hao Xu, Hui Pan, Lian Fang, Cangyuan Zhang, Chen Xiong, Weiti Cai
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Biology Direct
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Online Access:https://doi.org/10.1186/s13062-024-00567-x
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author Hao Xu
Hui Pan
Lian Fang
Cangyuan Zhang
Chen Xiong
Weiti Cai
author_facet Hao Xu
Hui Pan
Lian Fang
Cangyuan Zhang
Chen Xiong
Weiti Cai
author_sort Hao Xu
collection DOAJ
description Abstract Hepatocellular carcinoma (HCC) ranks among the most lethal malignancies around the world. However, the current management strategies for predicting prognosis in HCC patients remain unreliable. Our study developed a robust prognostic model based on glutamine metabolism associated-genes (GMAGs), utilizing data from The Cancer Genome Atlas database. The prognostic values of model were validated through the databases of the Gene Expression Omnibus and International Cancer Genome Consortium via Kaplan‒Meier curves and receiver operating characteristic (ROC). The potential biological pathways associated with prognostic risk were investigated through different enrichment analysis, and Gene variation analysis. The correlation between prognostic model and therapeutic responses were analyzed. Quantitative real-time PCR (qRT-PCR) and cellular experiments were measured to analyze the GMAGs. Consequently, a prognostic model was constructed of 4 GMAGs (RRM1, RRM2, G6PD, and GPX7) through least absolute shrinkage and selection operator (LASSO) regression analysis. The Kaplan‒Meier curves and ROC curves showed a reliable predictive capacity of prognosis for HCC patients (p < 0.05). The enrichment analyses revealed a multitude of biological pathways that are significantly associated with cancer. Patients with high prognostic risk might be sensitive to immunotherapy (p < 0.05). The results of qRT-PCR revealed that all 4 GMAGs exhibited significantly higher expression levels in HCC samples compared to normal samples (p < 0.05). Moreover, the knockdown of RRM1 suppresses the progression of HCC cells. In this study, we developed a robust prognostic model for predicting the prognosis of HCC patients based on GMAGs, and identified RRM1 as a potential therapeutic target for HCC.
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spelling doaj-art-dc0062fd43de4c4e8989e378b57b8e192025-08-20T02:32:56ZengBMCBiology Direct1745-61502024-11-0119111410.1186/s13062-024-00567-xA glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinomaHao Xu0Hui Pan1Lian Fang2Cangyuan Zhang3Chen Xiong4Weiti Cai5Department of Hepatobiliary Surgery, Siyang HospitalDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Gastrointestinal Surgery, Pingxiang People’s Hospital of Jiangxi ProvinceDepartment of Hepatobiliary Surgery, Shandong Public Health Clinical CenterDalian Medical UniversityDepartment of Hepatobiliary Surgery, Siyang HospitalAbstract Hepatocellular carcinoma (HCC) ranks among the most lethal malignancies around the world. However, the current management strategies for predicting prognosis in HCC patients remain unreliable. Our study developed a robust prognostic model based on glutamine metabolism associated-genes (GMAGs), utilizing data from The Cancer Genome Atlas database. The prognostic values of model were validated through the databases of the Gene Expression Omnibus and International Cancer Genome Consortium via Kaplan‒Meier curves and receiver operating characteristic (ROC). The potential biological pathways associated with prognostic risk were investigated through different enrichment analysis, and Gene variation analysis. The correlation between prognostic model and therapeutic responses were analyzed. Quantitative real-time PCR (qRT-PCR) and cellular experiments were measured to analyze the GMAGs. Consequently, a prognostic model was constructed of 4 GMAGs (RRM1, RRM2, G6PD, and GPX7) through least absolute shrinkage and selection operator (LASSO) regression analysis. The Kaplan‒Meier curves and ROC curves showed a reliable predictive capacity of prognosis for HCC patients (p < 0.05). The enrichment analyses revealed a multitude of biological pathways that are significantly associated with cancer. Patients with high prognostic risk might be sensitive to immunotherapy (p < 0.05). The results of qRT-PCR revealed that all 4 GMAGs exhibited significantly higher expression levels in HCC samples compared to normal samples (p < 0.05). Moreover, the knockdown of RRM1 suppresses the progression of HCC cells. In this study, we developed a robust prognostic model for predicting the prognosis of HCC patients based on GMAGs, and identified RRM1 as a potential therapeutic target for HCC.https://doi.org/10.1186/s13062-024-00567-xGlutamineMetabolismHepatocellular carcinomaPrognostic model
spellingShingle Hao Xu
Hui Pan
Lian Fang
Cangyuan Zhang
Chen Xiong
Weiti Cai
A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
Biology Direct
Glutamine
Metabolism
Hepatocellular carcinoma
Prognostic model
title A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
title_full A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
title_fullStr A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
title_full_unstemmed A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
title_short A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
title_sort glutamine metabolish associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma
topic Glutamine
Metabolism
Hepatocellular carcinoma
Prognostic model
url https://doi.org/10.1186/s13062-024-00567-x
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