Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer
Abstract Background Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated. Methods A systematic pan-cancer analysis was conducted to assess the expressio...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Biological Procedures Online |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12575-022-00177-9 |
| _version_ | 1811197996175458304 |
|---|---|
| author | Jie Mei Yun Cai Rui Xu Xinqian Yu Xu Han Miaomiao Weng Lingyan Chen Tao Ma Tianshu Gao Fei Gao Tiansong Xia Yichao Zhu Yan Zhang |
| author_facet | Jie Mei Yun Cai Rui Xu Xinqian Yu Xu Han Miaomiao Weng Lingyan Chen Tao Ma Tianshu Gao Fei Gao Tiansong Xia Yichao Zhu Yan Zhang |
| author_sort | Jie Mei |
| collection | DOAJ |
| description | Abstract Background Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated. Methods A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). The correlation of ACE2 expression and immunological characteristics in the BC tumor microenvironment (TME) was evaluated. The role of ACE2 in predicting the response to therapeutic options was estimated. Moreover, the pharmacodynamic effect of angiotensin-(1–7) (Ang-1–7), the product of ACE2, on chemotherapy and immunotherapy was evaluated on the BALB/c mouse BC model. In addition, the plasma samples from BC patients receiving neoadjuvant chemotherapy were collected and subjected to the correlation analysis of the expression level of Ang-1–7 and the response to neoadjuvant chemotherapy. Results ACE2 was lowly expressed in BC tissues compared with that in adjacent tissues. Interestingly, ACE2 was shown the highest correlation with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB) in BC. In addition, a high level of ACE2 indicated a low response to endocrine therapy and a high response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. In the mouse model, Ang-1–7 sensitized mouse BC to the chemotherapy and anti-PD-1 immunotherapy, which revealed its significant anti-tumor effect. Moreover, a high plasma level of Ang-1–7 was associated with a better response to neoadjuvant chemotherapy. Conclusions ACE2 identifies immuno-hot tumors in BC, and its enzymatic product Ang-1–7 sensitizes BC to the chemotherapy and immunotherapy by remodeling the TME. |
| first_indexed | 2024-04-12T01:23:46Z |
| format | Article |
| id | doaj.art-ff41cf08093d417a8320e542ac63d371 |
| institution | Directory Open Access Journal |
| issn | 1480-9222 |
| language | English |
| last_indexed | 2024-04-12T01:23:46Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Procedures Online |
| spelling | doaj.art-ff41cf08093d417a8320e542ac63d3712022-12-22T03:53:42ZengBMCBiological Procedures Online1480-92222022-10-0124111610.1186/s12575-022-00177-9Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancerJie Mei0Yun Cai1Rui Xu2Xinqian Yu3Xu Han4Miaomiao Weng5Lingyan Chen6Tao Ma7Tianshu Gao8Fei Gao9Tiansong Xia10Yichao Zhu11Yan Zhang12Department of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical UniversityDepartment of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical UniversityThe First Clinical Medical College, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityJiangsu Breast Disease Center, the First Affiliated Hospital With Nanjing Medical UniversityJiangsu Breast Disease Center, the First Affiliated Hospital With Nanjing Medical UniversityDepartment of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical UniversityDepartment of Breast Surgery, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical UniversityWuxi Clinical Medical College, Nanjing Medical UniversityWuxi Clinical Medical College, Nanjing Medical UniversityJiangsu Breast Disease Center, the First Affiliated Hospital With Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical UniversityAbstract Background Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated. Methods A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). The correlation of ACE2 expression and immunological characteristics in the BC tumor microenvironment (TME) was evaluated. The role of ACE2 in predicting the response to therapeutic options was estimated. Moreover, the pharmacodynamic effect of angiotensin-(1–7) (Ang-1–7), the product of ACE2, on chemotherapy and immunotherapy was evaluated on the BALB/c mouse BC model. In addition, the plasma samples from BC patients receiving neoadjuvant chemotherapy were collected and subjected to the correlation analysis of the expression level of Ang-1–7 and the response to neoadjuvant chemotherapy. Results ACE2 was lowly expressed in BC tissues compared with that in adjacent tissues. Interestingly, ACE2 was shown the highest correlation with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB) in BC. In addition, a high level of ACE2 indicated a low response to endocrine therapy and a high response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. In the mouse model, Ang-1–7 sensitized mouse BC to the chemotherapy and anti-PD-1 immunotherapy, which revealed its significant anti-tumor effect. Moreover, a high plasma level of Ang-1–7 was associated with a better response to neoadjuvant chemotherapy. Conclusions ACE2 identifies immuno-hot tumors in BC, and its enzymatic product Ang-1–7 sensitizes BC to the chemotherapy and immunotherapy by remodeling the TME.https://doi.org/10.1186/s12575-022-00177-9ACE2Breast cancerTumor microenvironmentAng-1–7Immunotherapy |
| spellingShingle | Jie Mei Yun Cai Rui Xu Xinqian Yu Xu Han Miaomiao Weng Lingyan Chen Tao Ma Tianshu Gao Fei Gao Tiansong Xia Yichao Zhu Yan Zhang Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer Biological Procedures Online ACE2 Breast cancer Tumor microenvironment Ang-1–7 Immunotherapy |
| title | Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer |
| title_full | Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer |
| title_fullStr | Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer |
| title_full_unstemmed | Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer |
| title_short | Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer |
| title_sort | angiotensin converting enzyme 2 identifies immuno hot tumors suggesting angiotensin 1 7 as a sensitizer for chemotherapy and immunotherapy in breast cancer |
| topic | ACE2 Breast cancer Tumor microenvironment Ang-1–7 Immunotherapy |
| url | https://doi.org/10.1186/s12575-022-00177-9 |
| work_keys_str_mv | AT jiemei angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT yuncai angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT ruixu angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT xinqianyu angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT xuhan angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT miaomiaoweng angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT lingyanchen angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT taoma angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT tianshugao angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT feigao angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT tiansongxia angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT yichaozhu angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer AT yanzhang angiotensinconvertingenzyme2identifiesimmunohottumorssuggestingangiotensin17asasensitizerforchemotherapyandimmunotherapyinbreastcancer |