Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-re...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15465 |
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| author | Yuan Zhang Cong Zhang Kangjie Li Jielian Deng Hui Liu Guichuan Lai Biao Xie Xiaoni Zhong |
| author_facet | Yuan Zhang Cong Zhang Kangjie Li Jielian Deng Hui Liu Guichuan Lai Biao Xie Xiaoni Zhong |
| author_sort | Yuan Zhang |
| collection | DOAJ |
| description | Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-related molecular subtypes were identified by unsupervised consensus clustering. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were employed to further establish immune-related gene signatures (IRGS). An evaluation of immune cell infiltration, biological function, tumor mutation burden (TMB), predicted immunotherapy response, and drug sensitivity in ACC patients was conducted to elucidate the applicative efficacy of IRGS in precision therapy. ACC patients were divided into two molecular subtypes through consistent clustering. Furthermore, the 3-gene signature (including PRKCA, LTBP1, and BIRC5) based on two molecular subtypes demonstrated consistent prognostic efficacy across the TCGA and GEO datasets and emerged as an independent prognostic factor. The low-risk group exhibited heightened immune cell infiltration, TMB, and immune checkpoint inhibitors (ICIs), associated with a favorable prognosis. Pathways associated with drug metabolism, hormone regulation, and metabolism were activated in the low-risk group. In conclusion, our findings suggest IRGS can be used as an independent prognostic biomarker, providing a foundation for shaping future ACC immunotherapy strategies. |
| first_indexed | 2024-03-10T21:11:31Z |
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| id | doaj.art-2431d9ead51a4fd5bb153e01eaf1cac4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:11:31Z |
| publishDate | 2023-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2431d9ead51a4fd5bb153e01eaf1cac42023-11-19T16:47:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201546510.3390/ijms242015465Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised ClusteringYuan Zhang0Cong Zhang1Kangjie Li2Jielian Deng3Hui Liu4Guichuan Lai5Biao Xie6Xiaoni Zhong7Department of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaAdrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-related molecular subtypes were identified by unsupervised consensus clustering. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were employed to further establish immune-related gene signatures (IRGS). An evaluation of immune cell infiltration, biological function, tumor mutation burden (TMB), predicted immunotherapy response, and drug sensitivity in ACC patients was conducted to elucidate the applicative efficacy of IRGS in precision therapy. ACC patients were divided into two molecular subtypes through consistent clustering. Furthermore, the 3-gene signature (including PRKCA, LTBP1, and BIRC5) based on two molecular subtypes demonstrated consistent prognostic efficacy across the TCGA and GEO datasets and emerged as an independent prognostic factor. The low-risk group exhibited heightened immune cell infiltration, TMB, and immune checkpoint inhibitors (ICIs), associated with a favorable prognosis. Pathways associated with drug metabolism, hormone regulation, and metabolism were activated in the low-risk group. In conclusion, our findings suggest IRGS can be used as an independent prognostic biomarker, providing a foundation for shaping future ACC immunotherapy strategies.https://www.mdpi.com/1422-0067/24/20/15465adrenocortical carcinomaunsupervised clusteringimmune-related genessubtypebiomarkersprognosis |
| spellingShingle | Yuan Zhang Cong Zhang Kangjie Li Jielian Deng Hui Liu Guichuan Lai Biao Xie Xiaoni Zhong Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering International Journal of Molecular Sciences adrenocortical carcinoma unsupervised clustering immune-related genes subtype biomarkers prognosis |
| title | Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering |
| title_full | Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering |
| title_fullStr | Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering |
| title_full_unstemmed | Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering |
| title_short | Identification of Molecular Subtypes and Prognostic Characteristics of Adrenocortical Carcinoma Based on Unsupervised Clustering |
| title_sort | identification of molecular subtypes and prognostic characteristics of adrenocortical carcinoma based on unsupervised clustering |
| topic | adrenocortical carcinoma unsupervised clustering immune-related genes subtype biomarkers prognosis |
| url | https://www.mdpi.com/1422-0067/24/20/15465 |
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