A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma
Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.796681/full |
| _version_ | 1811293590667657216 |
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| author | Yuanyuan Deng Huihuang Li Jinglan Fu Ying Pu Ying Zhang Shijing Chen Shiyu Tong Huixia Liu |
| author_facet | Yuanyuan Deng Huihuang Li Jinglan Fu Ying Pu Ying Zhang Shijing Chen Shiyu Tong Huixia Liu |
| author_sort | Yuanyuan Deng |
| collection | DOAJ |
| description | Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to invasion, metastasis, and drug resistance. This study aimed to reveal the role of hypoxia in Adrenocortical carcinoma and develop a hypoxia risk score (HRS) for Adrenocortical carcinoma prognostic prediction.Methods: Hypoxia-related genes were obtained from the Molecular Signatures Database. The training cohorts of patients with adrenocortical carcinoma were downloaded from The Cancer Genome Atlas, while another three validation cohorts with comprehensive survival data were collected from the Gene Expression Omnibus. In addition, we constructed a hypoxia classifier using a random survival forest model. Moreover, we explored the relationship between the hypoxia risk score and immunophenotype in adrenocortical carcinoma to evaluate the efficacy of immune check inhibitors (ICI) therapy and prognosis of patients.Results: HRS and tumor stage were identified as independent prognostic factors. HRS was negatively correlated with immune cycle activity, immune cell infiltration, and the T cell inflammatory score. Therefore, we considered the low hypoxia risk score group as the inflammatory immunophenotype, whereas the high HRS group was a non-inflammatory immunophenotype. In addition, the HRS was negatively related to the expression of common immune checkpoint molecules such as PD-L1, CD200, CTLA-4, and TIGIT, suggesting that patients with a lower hypoxia risk score respond better to immunotherapy.Conclusion: We developed and validated a novel hypoxia risk score to predict the immunophenotype and response of patients with adrenocortical carcinoma to immune check inhibitors therapy. These findings not only provide fresh prognostic indicators for adrenocortical carcinoma but also offer several promising treatment targets for this disease. |
| first_indexed | 2024-04-13T05:03:42Z |
| format | Article |
| id | doaj.art-a849d7d92d5b4bd7b1596445e3fc6570 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T05:03:42Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a849d7d92d5b4bd7b1596445e3fc65702022-12-22T03:01:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-12-011310.3389/fgene.2022.796681796681A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinomaYuanyuan Deng0Huihuang Li1Jinglan Fu2Ying Pu3Ying Zhang4Shijing Chen5Shiyu Tong6Huixia Liu7Department of Geriatric Endocrine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatric Endocrine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatric Endocrine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatric Endocrine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatric Endocrine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatric Endocrine, Xiangya Hospital, Central South University, Changsha, ChinaBackground: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to invasion, metastasis, and drug resistance. This study aimed to reveal the role of hypoxia in Adrenocortical carcinoma and develop a hypoxia risk score (HRS) for Adrenocortical carcinoma prognostic prediction.Methods: Hypoxia-related genes were obtained from the Molecular Signatures Database. The training cohorts of patients with adrenocortical carcinoma were downloaded from The Cancer Genome Atlas, while another three validation cohorts with comprehensive survival data were collected from the Gene Expression Omnibus. In addition, we constructed a hypoxia classifier using a random survival forest model. Moreover, we explored the relationship between the hypoxia risk score and immunophenotype in adrenocortical carcinoma to evaluate the efficacy of immune check inhibitors (ICI) therapy and prognosis of patients.Results: HRS and tumor stage were identified as independent prognostic factors. HRS was negatively correlated with immune cycle activity, immune cell infiltration, and the T cell inflammatory score. Therefore, we considered the low hypoxia risk score group as the inflammatory immunophenotype, whereas the high HRS group was a non-inflammatory immunophenotype. In addition, the HRS was negatively related to the expression of common immune checkpoint molecules such as PD-L1, CD200, CTLA-4, and TIGIT, suggesting that patients with a lower hypoxia risk score respond better to immunotherapy.Conclusion: We developed and validated a novel hypoxia risk score to predict the immunophenotype and response of patients with adrenocortical carcinoma to immune check inhibitors therapy. These findings not only provide fresh prognostic indicators for adrenocortical carcinoma but also offer several promising treatment targets for this disease.https://www.frontiersin.org/articles/10.3389/fgene.2022.796681/fullAdrenocortical carcinomahypoxiarisk scoretumor microenvironmentimmunotherapy |
| spellingShingle | Yuanyuan Deng Huihuang Li Jinglan Fu Ying Pu Ying Zhang Shijing Chen Shiyu Tong Huixia Liu A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma Frontiers in Genetics Adrenocortical carcinoma hypoxia risk score tumor microenvironment immunotherapy |
| title | A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma |
| title_full | A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma |
| title_fullStr | A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma |
| title_full_unstemmed | A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma |
| title_short | A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma |
| title_sort | hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma |
| topic | Adrenocortical carcinoma hypoxia risk score tumor microenvironment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.796681/full |
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