The potential role of abnormal angiotensin-converting enzyme 2 expression correlated with immune infiltration after SARS-CoV-2 infection in the prognosis of breast cancer

Jiang, Yufeng; Chen, Ling; Shen, Jinsheng; Mei, Xiaofei; Yao, Jialu; Tan, Cheng; Zhou, Yafeng

doi:10.18632/aging.203418

Cited by 4 publications

(6 citation statements)

References 30 publications

(26 reference statements)

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“…Nevertheless, in patients receiving chemotherapy, elevated ACE2 was correlated with worse RFS and DMFS compared with patients with low ACE2 expression. This finding is inconsistent with the result reported in a recent publication showing that elevated ACE2 immunostaining is unrelated to the outcome in nonspecific types of invasive breast cancer [ 49 ]. This inconsistency may be due to the fact that the aforementioned study only focused on the expression level of ACE2, but did not include the treatment modality of the patients.…”

Section: Discussioncontrasting

confidence: 99%

“…Our findings also imply that upregulation of ACE2 in cancer tissues with originally low ACE2 expression may be a driver of cancer progression. This possibility is partly supported by a recent study showing that higher ACE2 expression appears to be associated with higher histological grade, HER2-enriched and Basal-like subtypes [ 49 ]. These indicators are known to be associated with poor prognosis in breast cancer.…”

Section: Discussionmentioning

confidence: 78%

“…Nevertheless, other studies have reported opposite results that ACE2 upregulation promotes tumor progression, and even that ACE2 may play distinct roles in different subtypes of the same tumor [ 47 , 48 ]. This feature seems to be more pronounced in breast cancer [ 24 , 49 , 50 ]. Despite previous studies have reported the relationship between ACE2 expression and breast cancer prognosis, a systemic investigation of the association between ACE2 expression and chemotherapy and prognosis is still lacking.…”

Section: Discussionmentioning

confidence: 99%

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Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy

et al. 2022

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Background Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system and a well-known functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The COVID-19 pandemic has brought ACE2 into the spotlight, and ACE2 expression in tumors and its relationship with SARS-COV-2 infection and prognosis of cancer patients have received extensive attention. However, the association between ACE2 expression and tumor therapy and prognosis, especially in breast cancer, remains ambiguous and requires further investigation. We have previously reported that ACE2 is elevated in drug-resistant breast cancer cells, but the exact function of ACE2 in drug resistance and progression of this malignant disease has not been explored. Methods The expression of ACE2 and HIF-1α in parental and drug-resistant breast cancer cells under normoxic and hypoxic conditions was analyzed by Western blot and qRT-PCR methods. The protein levels of ACE2 in plasma samples from breast cancer patients were examined by ELISA. The relationship between ACE2 expression and breast cancer treatment and prognosis was analyzed using clinical specimens and public databases. The reactive oxygen species (ROS) levels in breast cancer cells were measured by using a fluorescent probe. Small interfering RNAs (siRNAs) or lentivirus-mediated shRNA was used to silence ACE2 and HIF-1α expression in cellular models. The effect of ACE2 knockdown on drug resistance in breast cancer was determined by Cell Counting Kit 8 (CCK-8)-based assay, colony formation assay, apoptosis and EdU assay. Results ACE2 expression is relatively low in breast cancer cells, but increases rapidly and specifically after exposure to anticancer drugs, and remains high after resistance is acquired. Mechanistically, chemotherapeutic agents increase ACE2 expression in breast cancer cells by inducing intracellular ROS production, and increased ROS levels enhance AKT phosphorylation and subsequently increase HIF-1α expression, which in turn upregulates ACE2 expression. Although ACE2 levels in plasma and cancer tissues are lower in breast cancer patients compared with healthy controls, elevated ACE2 in patients after chemotherapy is a predictor of poor treatment response and an unfavorable prognostic factor for survival in breast cancer patients. Conclusion ACE2 is a gene in breast cancer cells that responds rapidly to chemotherapeutic agents through the ROS-AKT-HIF-1α axis. Elevated ACE2 modulates the sensitivity of breast cancer cells to anticancer drugs by optimizing the balance of intracellular ROS. Moreover, increased ACE2 is not only a predictor of poor response to chemotherapy, but is also associated with a worse prognosis in breast cancer patients. Thus, our findings provide novel insights into the spatiotemporal differences in the function of ACE2 in the initiation and progression of breast cancer.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

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Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy

et al. 2022

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“…Jiang et al. suggested that breast tumor tissues can be further reduced at ACE2 expression level (angiotensin-converting enzyme 2) after SARS-CoV-2 infection, which further deteriorates immune infiltration and worsens the prognosis of luminal B breast cancer after SARS-CoV-2 infection ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cluster 2: Recovery of breast cancer patients in the pandemic A paper suggested that the treatment of ACEIs (angiotensinconverting enzyme ACE inhibitors) in Luminal A breast cancer might facilitate tumor progression (44). Jiang et al suggested that breast tumor tissues can be further reduced at ACE2 expression level (angiotensin-converting enzyme 2) after SARS-CoV-2 infection, which further deteriorates immune infiltration and worsens the prognosis of luminal B breast cancer after SARS-CoV-2 infection (45).…”

Section: Cluster 1: Breast Cancer Surgery In the Pandemicmentioning

confidence: 99%

Research trends and hotspots of breast cancer management during the COVID-19 pandemic: A bibliometric analysis

Lyu

Tang

et al. 2022

Front. Oncol.

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BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is disrupting routine medical care of cancer patients, including those who have cancer or are undergoing cancer screening. In this study, breast cancer management during the COVID-19 pandemic (BCMP) is reviewed, and the research trends of BCMP are evaluated by quantitative and qualitative evaluation.MethodsIn this study, published studies relating to BCMP from 1 January 2020 to 1 April 2022 were searched from the Web of Science database (WoS). Bibliometric indicators consisted of publications, research hotspots, keywords, authors, journals, institutions, nations, and h-index.ResultsA total of 182 articles investigating BCMP were searched. The United States of America and the University of Rome Tor Vergata were the nation and the institution with the most publications on BCMP. The first three periodicals with leading published BCMP studies were Breast Cancer Research and Treatment, Breast, and In Vivo. Buonomo OC was the most prolific author in this field, publishing nine articles (9/182, 4.94%). The co-keywords analysis of BCMP suggests that the top hotspots and trends in research are screening, surgery, rehabilitation, emotion, diagnosis, treatment, and vaccine management of breast cancer during the pandemic. The hotspot words were divided into six clusters, namely, screening for breast cancer patients in the pandemic, breast cancer surgery in the pandemic, recovery of breast cancer patients in the pandemic, motion effect of the outbreak on breast cancer patients, diagnosis and treatment of breast cancer patients in the pandemic, and vaccination management for breast cancer patients during a pandemic.ConclusionBCMP has received attention from scholars in many nations over the last 3 years. This study revealed significant contributions to BCMP research by nations, institutions, scholars, and journals. The stratified clustering study provided the current status and future trends of BCMP to help physicians with the diagnosis and treatment of breast cancer through the pandemic, and provide a reference for in-depth clinical studies on BCMP.

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The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study

Jacobs,

Helder,

Albers

et al. 2024

Breast Cancer Res

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Background Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival. Methods In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20). Results Ex vivo cytokine production capacity of TNF, IL-6 and IL-1β was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1β after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1β and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively). Conclusions This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

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The potential role of abnormal angiotensin-converting enzyme 2 expression correlated with immune infiltration after SARS-CoV-2 infection in the prognosis of breast cancer

Cited by 4 publications

References 30 publications

Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy

Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy

Research trends and hotspots of breast cancer management during the COVID-19 pandemic: A bibliometric analysis

The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study

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