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Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma

Peroxisome proliferator-activated receptor gamma (PPARG), a key transcription factor involved in lipid metabolism and glucose homeostasis, has been implicated in various types of cancer. However, its precise role in cancer remains unclear. In this study, we conducted a comprehensive pan-cancer analy...

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Autores principales: Ran, Yunsheng, Hu, Chujiao, Wan, Junzhao, Kang, Qian, Zhou, Ruixian, Liu, Ping, Ma, Dan, Wang, Jianta, Tang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690586/
https://www.ncbi.nlm.nih.gov/pubmed/38044948
http://dx.doi.org/10.3389/fphar.2023.1298341
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author Ran, Yunsheng
Hu, Chujiao
Wan, Junzhao
Kang, Qian
Zhou, Ruixian
Liu, Ping
Ma, Dan
Wang, Jianta
Tang, Lei
author_facet Ran, Yunsheng
Hu, Chujiao
Wan, Junzhao
Kang, Qian
Zhou, Ruixian
Liu, Ping
Ma, Dan
Wang, Jianta
Tang, Lei
author_sort Ran, Yunsheng
collection PubMed
description Peroxisome proliferator-activated receptor gamma (PPARG), a key transcription factor involved in lipid metabolism and glucose homeostasis, has been implicated in various types of cancer. However, its precise role in cancer remains unclear. In this study, we conducted a comprehensive pan-cancer analysis of PPARG expression using various types of cancer obtained from public databases. We observed significant heterogeneity in PPARG expression across different types of cancer. The association between PPARG expression and patient prognosis was investigated using Cox proportional hazards regression models and survival analysis. Clinical features and protein expression levels in the cohort showed that PPARG expression was strongly associated, suggesting its potential as a therapeutic target. We also evaluated the prognostic potential of PPARG by analyzing immune infiltration and genomic stability. We experimentally validated the potential of PPARG as a therapeutic target by analyzing drug sensitivity profiles, molecular docking simulations, and in vitro cell proliferation assays associated with PPARG expression. We identified common expression patterns of PPARG with other genes involved in key carcinogenic pathways. This provides deeper insights into the molecular mechanisms underlying its carcinogenic role. Additionally, functional enrichment analysis revealed significant enrichment of genes related to drug metabolism, cell proliferation, and immune response pathways associated with PPARG. Our findings highlight the importance of PPARG in the broader biology of cancer and suggest its potential as a diagnostic and therapeutic target for specific types of cancer. The results of our study provide strong support for the potential role of PPARG as a promising prognostic biomarker and immunotherapeutic target across various types of cancer.
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spelling pubmed-106905862023-12-02 Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma Ran, Yunsheng Hu, Chujiao Wan, Junzhao Kang, Qian Zhou, Ruixian Liu, Ping Ma, Dan Wang, Jianta Tang, Lei Front Pharmacol Pharmacology Peroxisome proliferator-activated receptor gamma (PPARG), a key transcription factor involved in lipid metabolism and glucose homeostasis, has been implicated in various types of cancer. However, its precise role in cancer remains unclear. In this study, we conducted a comprehensive pan-cancer analysis of PPARG expression using various types of cancer obtained from public databases. We observed significant heterogeneity in PPARG expression across different types of cancer. The association between PPARG expression and patient prognosis was investigated using Cox proportional hazards regression models and survival analysis. Clinical features and protein expression levels in the cohort showed that PPARG expression was strongly associated, suggesting its potential as a therapeutic target. We also evaluated the prognostic potential of PPARG by analyzing immune infiltration and genomic stability. We experimentally validated the potential of PPARG as a therapeutic target by analyzing drug sensitivity profiles, molecular docking simulations, and in vitro cell proliferation assays associated with PPARG expression. We identified common expression patterns of PPARG with other genes involved in key carcinogenic pathways. This provides deeper insights into the molecular mechanisms underlying its carcinogenic role. Additionally, functional enrichment analysis revealed significant enrichment of genes related to drug metabolism, cell proliferation, and immune response pathways associated with PPARG. Our findings highlight the importance of PPARG in the broader biology of cancer and suggest its potential as a diagnostic and therapeutic target for specific types of cancer. The results of our study provide strong support for the potential role of PPARG as a promising prognostic biomarker and immunotherapeutic target across various types of cancer. Frontiers Media S.A. 2023-11-15 /pmc/articles/PMC10690586/ /pubmed/38044948 http://dx.doi.org/10.3389/fphar.2023.1298341 Text en Copyright © 2023 Ran, Hu, Wan, Kang, Zhou, Liu, Ma, Wang and Tang. 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 Pharmacology
Ran, Yunsheng
Hu, Chujiao
Wan, Junzhao
Kang, Qian
Zhou, Ruixian
Liu, Ping
Ma, Dan
Wang, Jianta
Tang, Lei
Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
title Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
title_full Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
title_fullStr Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
title_full_unstemmed Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
title_short Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
title_sort integrated investigation and experimental validation of pparg as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690586/
https://www.ncbi.nlm.nih.gov/pubmed/38044948
http://dx.doi.org/10.3389/fphar.2023.1298341
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