The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma
Abstract 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 characteri...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Diagnostic Pathology |
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| Online Access: | https://doi.org/10.1186/s13000-023-01384-y |
| _version_ | 1797578531478175744 |
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| author | Yang Yang Jiayu Liang Junjie Zhao Xinyuan Wang Dechao Feng Hang Xu Yu Shen Yaowen Zhang Jindong Dai Zhipeng Wang Qiang Wei Zhenhua Liu |
| author_facet | Yang Yang Jiayu Liang Junjie Zhao Xinyuan Wang Dechao Feng Hang Xu Yu Shen Yaowen Zhang Jindong Dai Zhipeng Wang Qiang Wei Zhenhua Liu |
| author_sort | Yang Yang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T22:23:11Z |
| format | Article |
| id | doaj.art-5ab628ad93194e81a229b123bee44250 |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-03-10T22:23:11Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-5ab628ad93194e81a229b123bee442502023-11-19T12:12:25ZengBMCDiagnostic Pathology1746-15962023-08-0118111710.1186/s13000-023-01384-yThe multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinomaYang Yang0Jiayu Liang1Junjie Zhao2Xinyuan Wang3Dechao Feng4Hang Xu5Yu Shen6Yaowen Zhang7Jindong Dai8Zhipeng Wang9Qiang Wei10Zhenhua Liu11Department of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityAbstract 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.https://doi.org/10.1186/s13000-023-01384-yACSL1Clear cell renal cell carcinomaMethylationImmune Microenvironmentm6A modification |
| spellingShingle | Yang Yang Jiayu Liang Junjie Zhao Xinyuan Wang Dechao Feng Hang Xu Yu Shen Yaowen Zhang Jindong Dai Zhipeng Wang Qiang Wei Zhenhua Liu The multi-omics analyses of acsl1 reveal its translational significance as a tumor microenvironmental and prognostic biomarker in clear cell renal cell carcinoma Diagnostic Pathology ACSL1 Clear cell renal cell carcinoma Methylation Immune Microenvironment m6A modification |
| 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 | ACSL1 Clear cell renal cell carcinoma Methylation Immune Microenvironment m6A modification |
| url | https://doi.org/10.1186/s13000-023-01384-y |
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