The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas
Increasing evidence confirms that tumor microenvironment (TME) can influence tumor progression and treatment, but TME is still understudied in adrenocortical carcinoma (ACC). In this study, we first scored TME using the xCell algorithm, then defined genes associated with TME, and then used consensus...
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MDPI AG
2023-02-01
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Online Access: | https://www.mdpi.com/2073-4409/12/5/755 |
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author | Guichuan Lai Hui Liu Jielian Deng Kangjie Li Cong Zhang Xiaoni Zhong Biao Xie |
author_facet | Guichuan Lai Hui Liu Jielian Deng Kangjie Li Cong Zhang Xiaoni Zhong Biao Xie |
author_sort | Guichuan Lai |
collection | DOAJ |
description | Increasing evidence confirms that tumor microenvironment (TME) can influence tumor progression and treatment, but TME is still understudied in adrenocortical carcinoma (ACC). In this study, we first scored TME using the xCell algorithm, then defined genes associated with TME, and then used consensus unsupervised clustering analysis to construct TME-related subtypes. Meanwhile, weighted gene co-expression network analysis was used to identify modules correlated with TME-related subtypes. Ultimately, the LASSO-Cox approach was used to establish a TME-related signature. The results showed that TME-related scores in ACC may not correlate with clinical features but do promote a better overall survival. Patients were classified into two TME-related subtypes. Subtype 2 had more immune signaling features, higher expression of immune checkpoints and MHC molecules, no CTNNB1 mutations, higher infiltration of macrophages and endothelial cells, lower tumor immune dysfunction and exclusion scores, and higher immunophenoscore, suggesting that subtype 2 may be more sensitive to immunotherapy. 231 modular genes highly relevant to TME-related subtypes were identified, and a 7-gene TME-related signature that independently predicted patient prognosis was established. Our study revealed an integrated role of TME in ACC and helped to identify those patients who really responded to immunotherapy, while providing new strategies on risk management and prognosis prediction. |
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language | English |
last_indexed | 2024-03-11T07:28:26Z |
publishDate | 2023-02-01 |
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spelling | doaj.art-293450846c224519a2be4895eb40e07f2023-11-17T07:27:43ZengMDPI AGCells2073-44092023-02-0112575510.3390/cells12050755The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical CarcinomasGuichuan Lai0Hui Liu1Jielian Deng2Kangjie Li3Cong Zhang4Xiaoni Zhong5Biao Xie6Department 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, ChinaIncreasing evidence confirms that tumor microenvironment (TME) can influence tumor progression and treatment, but TME is still understudied in adrenocortical carcinoma (ACC). In this study, we first scored TME using the xCell algorithm, then defined genes associated with TME, and then used consensus unsupervised clustering analysis to construct TME-related subtypes. Meanwhile, weighted gene co-expression network analysis was used to identify modules correlated with TME-related subtypes. Ultimately, the LASSO-Cox approach was used to establish a TME-related signature. The results showed that TME-related scores in ACC may not correlate with clinical features but do promote a better overall survival. Patients were classified into two TME-related subtypes. Subtype 2 had more immune signaling features, higher expression of immune checkpoints and MHC molecules, no CTNNB1 mutations, higher infiltration of macrophages and endothelial cells, lower tumor immune dysfunction and exclusion scores, and higher immunophenoscore, suggesting that subtype 2 may be more sensitive to immunotherapy. 231 modular genes highly relevant to TME-related subtypes were identified, and a 7-gene TME-related signature that independently predicted patient prognosis was established. Our study revealed an integrated role of TME in ACC and helped to identify those patients who really responded to immunotherapy, while providing new strategies on risk management and prognosis prediction.https://www.mdpi.com/2073-4409/12/5/755adrenocortical carcinomatumor microenvironmentimmunotherapysubtypebioinformaticsrisk stratification |
spellingShingle | Guichuan Lai Hui Liu Jielian Deng Kangjie Li Cong Zhang Xiaoni Zhong Biao Xie The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas Cells adrenocortical carcinoma tumor microenvironment immunotherapy subtype bioinformatics risk stratification |
title | The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas |
title_full | The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas |
title_fullStr | The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas |
title_full_unstemmed | The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas |
title_short | The Characteristics of Tumor Microenvironment Predict Survival and Response to Immunotherapy in Adrenocortical Carcinomas |
title_sort | characteristics of tumor microenvironment predict survival and response to immunotherapy in adrenocortical carcinomas |
topic | adrenocortical carcinoma tumor microenvironment immunotherapy subtype bioinformatics risk stratification |
url | https://www.mdpi.com/2073-4409/12/5/755 |
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