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...

Full description

Bibliographic Details
Main Authors: Guichuan Lai, Hui Liu, Jielian Deng, Kangjie Li, Cong Zhang, Xiaoni Zhong, Biao Xie
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/5/755
_version_ 1797615567445688320
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.
first_indexed 2024-03-11T07:28:26Z
format Article
id doaj.art-293450846c224519a2be4895eb40e07f
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-11T07:28:26Z
publishDate 2023-02-01
publisher MDPI AG
record_format Article
series Cells
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
work_keys_str_mv AT guichuanlai thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT huiliu thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT jieliandeng thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT kangjieli thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT congzhang thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT xiaonizhong thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT biaoxie thecharacteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT guichuanlai characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT huiliu characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT jieliandeng characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT kangjieli characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT congzhang characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT xiaonizhong characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas
AT biaoxie characteristicsoftumormicroenvironmentpredictsurvivalandresponsetoimmunotherapyinadrenocorticalcarcinomas