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The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of kidney cancer. Dysregulation of long-chain acyl-CoA synthetase 1 (ACSL1) is strongly implicated in undesirable results in varieties of cancers. Nevertheless, the dysregulation and associated multi-omics characteristics of...

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Autores principales: Yang, Yang, Liang, Jiayu, Zhao, Junjie, Wang, Xinyuan, Feng, Dechao, Xu, Hang, Shen, Yu, Zhang, Yaowen, Dai, Jindong, Wang, Zhipeng, Wei, Qiang, Liu, Zhenhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463412/
https://www.ncbi.nlm.nih.gov/pubmed/37608295
http://dx.doi.org/10.1186/s13000-023-01384-y
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author Yang, Yang
Liang, Jiayu
Zhao, Junjie
Wang, Xinyuan
Feng, Dechao
Xu, Hang
Shen, Yu
Zhang, Yaowen
Dai, Jindong
Wang, Zhipeng
Wei, Qiang
Liu, Zhenhua
author_facet Yang, Yang
Liang, Jiayu
Zhao, Junjie
Wang, Xinyuan
Feng, Dechao
Xu, Hang
Shen, Yu
Zhang, Yaowen
Dai, Jindong
Wang, Zhipeng
Wei, Qiang
Liu, Zhenhua
author_sort Yang, Yang
collection PubMed
description BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of kidney cancer. Dysregulation of long-chain acyl-CoA synthetase 1 (ACSL1) is strongly implicated in undesirable results in varieties of cancers. Nevertheless, the dysregulation and associated multi-omics characteristics of ACSL1 in ccRCC remain elusive. METHODS: We probed the mRNA and protein profiles of ACSL1 in RCC using data from the Cancer Genome Atlas, Gene Expression Omnibus, the Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort and RCC cell lines. Correlations between ACSL1 expression and clinicopathological features, epigenetic modification and immune microenvironment characteristics were analyzed to reveal the multi-omics profile associated with ACSL1. RESULTS: ACSL1 was down-regulated in ccRCC tissues compared to adjacent normal tissues. Lower expression of ACSL1 was linked to unfavorable pathological parameters and prognosis. The dysregulation of ACSL1 was greatly ascribed to CpG island-associated methylation modification. The ACSL1 high-expression subgroup had enriched fatty acid metabolism-related pathways and high expression of ferroptosis-related genes. In contrast, the ACSL1 low-expression subgroup exhibited higher immune and microenvironment scores, elevated expression of immune checkpoints PDCD1, CTLA4, LAG3, and TIGIT, and higher TIDE scores. Using data from the GDSC database, we corroborated that down-regulation of ACSL1 was associated with higher sensitivity towards Erlotinib, Pazopanib, and PI3K-Akt-mTOR-targeted therapeutic strategies. CONCLUSION: Taken together, our findings point to ACSL1 as a biomarker for prognostic prediction of ccRCC, identifying the tumor microenvironment (TME) phenotype, and even contributing to treatment decision-making in ccRCC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13000-023-01384-y.
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spelling pubmed-104634122023-08-30 The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma Yang, Yang Liang, Jiayu Zhao, Junjie Wang, Xinyuan Feng, Dechao Xu, Hang Shen, Yu Zhang, Yaowen Dai, Jindong Wang, Zhipeng Wei, Qiang Liu, Zhenhua Diagn Pathol Research BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of kidney cancer. Dysregulation of long-chain acyl-CoA synthetase 1 (ACSL1) is strongly implicated in undesirable results in varieties of cancers. Nevertheless, the dysregulation and associated multi-omics characteristics of ACSL1 in ccRCC remain elusive. METHODS: We probed the mRNA and protein profiles of ACSL1 in RCC using data from the Cancer Genome Atlas, Gene Expression Omnibus, the Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort and RCC cell lines. Correlations between ACSL1 expression and clinicopathological features, epigenetic modification and immune microenvironment characteristics were analyzed to reveal the multi-omics profile associated with ACSL1. RESULTS: ACSL1 was down-regulated in ccRCC tissues compared to adjacent normal tissues. Lower expression of ACSL1 was linked to unfavorable pathological parameters and prognosis. The dysregulation of ACSL1 was greatly ascribed to CpG island-associated methylation modification. The ACSL1 high-expression subgroup had enriched fatty acid metabolism-related pathways and high expression of ferroptosis-related genes. In contrast, the ACSL1 low-expression subgroup exhibited higher immune and microenvironment scores, elevated expression of immune checkpoints PDCD1, CTLA4, LAG3, and TIGIT, and higher TIDE scores. Using data from the GDSC database, we corroborated that down-regulation of ACSL1 was associated with higher sensitivity towards Erlotinib, Pazopanib, and PI3K-Akt-mTOR-targeted therapeutic strategies. CONCLUSION: Taken together, our findings point to ACSL1 as a biomarker for prognostic prediction of ccRCC, identifying the tumor microenvironment (TME) phenotype, and even contributing to treatment decision-making in ccRCC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13000-023-01384-y. BioMed Central 2023-08-22 /pmc/articles/PMC10463412/ /pubmed/37608295 http://dx.doi.org/10.1186/s13000-023-01384-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Yang
Liang, Jiayu
Zhao, Junjie
Wang, Xinyuan
Feng, Dechao
Xu, Hang
Shen, Yu
Zhang, Yaowen
Dai, Jindong
Wang, Zhipeng
Wei, Qiang
Liu, Zhenhua
The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
title The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
title_full The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
title_fullStr The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
title_full_unstemmed The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
title_short The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
title_sort multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463412/
https://www.ncbi.nlm.nih.gov/pubmed/37608295
http://dx.doi.org/10.1186/s13000-023-01384-y
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