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A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma
BACKGROUND: Hepatocellular carcinoma (HCC), one of the highest causes of cancer-associated death, has effective treatments, especially for patients with advanced HCC. Circadian rhythm participates in several important physiological functions, and its chronic disruption results in many disordered dis...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643945/ https://www.ncbi.nlm.nih.gov/pubmed/37969365 http://dx.doi.org/10.21037/tcr-23-217 |
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author | Liang, Qing Ye, Yongqing Li, Enze Fan, Jingming Gong, Jinglin Ying, Jiaxin Cao, Yawen Li, Rongqi Wang, Ping |
author_facet | Liang, Qing Ye, Yongqing Li, Enze Fan, Jingming Gong, Jinglin Ying, Jiaxin Cao, Yawen Li, Rongqi Wang, Ping |
author_sort | Liang, Qing |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC), one of the highest causes of cancer-associated death, has effective treatments, especially for patients with advanced HCC. Circadian rhythm participates in several important physiological functions, and its chronic disruption results in many disordered diseases, including cancer. However, the role of circadian rhythm in the overall survival (OS) of patients with HCC remains unclear. METHODS: We investigated the expression, copy number variation (CNV), and mutation profiles of core circadian clock genes in normal and tumor tissues. We developed and validated a messenger RNA signature (mRNASig) based on prognostic circadian clock genes. A set of bioinformatic tools were applied for functional annotation and tumor-associated microenvironment (TME) analysis. RESULTS: Core circadian clock genes were disrupted in terms of the transcription and CNV of HCC samples. The mRNASig, including NPAS2, NR1D1, PER1, RORC, and TIMELESS, was constructed. We divided patients with HCC into high-risk group and low-risk group based on the median value of the risk score. The high-risk group had a poorer prognosis than the low-risk group. The high-risk group was associated with malignant processes (e.g., proliferation, oncogenic pathway, DNA repair), metabolism, and tumor mutational burden (TMB). Surprisingly, the low-risk group was associated with enriched angiogenesis and was linked to enhanced response to sorafenib. Moreover, the high-risk group showed poor infiltration of CD8 T cells and natural killer cells accompanied by higher expression of CTLA4, PDCD1, TIGIT, and TIM3. Additionally, the mRNASig was associated with TMB. CONCLUSIONS: The mRNASig based on core circadian clock genes is a potential prognostic signature and therapeutic strategy and is significantly associated with the malignant biology of HCC. |
format | Online Article Text |
id | pubmed-10643945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-106439452023-11-15 A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma Liang, Qing Ye, Yongqing Li, Enze Fan, Jingming Gong, Jinglin Ying, Jiaxin Cao, Yawen Li, Rongqi Wang, Ping Transl Cancer Res Original Article BACKGROUND: Hepatocellular carcinoma (HCC), one of the highest causes of cancer-associated death, has effective treatments, especially for patients with advanced HCC. Circadian rhythm participates in several important physiological functions, and its chronic disruption results in many disordered diseases, including cancer. However, the role of circadian rhythm in the overall survival (OS) of patients with HCC remains unclear. METHODS: We investigated the expression, copy number variation (CNV), and mutation profiles of core circadian clock genes in normal and tumor tissues. We developed and validated a messenger RNA signature (mRNASig) based on prognostic circadian clock genes. A set of bioinformatic tools were applied for functional annotation and tumor-associated microenvironment (TME) analysis. RESULTS: Core circadian clock genes were disrupted in terms of the transcription and CNV of HCC samples. The mRNASig, including NPAS2, NR1D1, PER1, RORC, and TIMELESS, was constructed. We divided patients with HCC into high-risk group and low-risk group based on the median value of the risk score. The high-risk group had a poorer prognosis than the low-risk group. The high-risk group was associated with malignant processes (e.g., proliferation, oncogenic pathway, DNA repair), metabolism, and tumor mutational burden (TMB). Surprisingly, the low-risk group was associated with enriched angiogenesis and was linked to enhanced response to sorafenib. Moreover, the high-risk group showed poor infiltration of CD8 T cells and natural killer cells accompanied by higher expression of CTLA4, PDCD1, TIGIT, and TIM3. Additionally, the mRNASig was associated with TMB. CONCLUSIONS: The mRNASig based on core circadian clock genes is a potential prognostic signature and therapeutic strategy and is significantly associated with the malignant biology of HCC. AME Publishing Company 2023-10-24 2023-10-31 /pmc/articles/PMC10643945/ /pubmed/37969365 http://dx.doi.org/10.21037/tcr-23-217 Text en 2023 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Liang, Qing Ye, Yongqing Li, Enze Fan, Jingming Gong, Jinglin Ying, Jiaxin Cao, Yawen Li, Rongqi Wang, Ping A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
title | A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
title_full | A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
title_fullStr | A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
title_full_unstemmed | A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
title_short | A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
title_sort | circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643945/ https://www.ncbi.nlm.nih.gov/pubmed/37969365 http://dx.doi.org/10.21037/tcr-23-217 |
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