High expression of ACE2 in HER2 subtype of breast cancer is a marker of poor prognosis

Nair, Madhumathy G.; Prabhu, Jyothi S; Sridhar, T.

doi:10.1016/j.ctarc.2021.100321

Cited by 11 publications

(16 citation statements)

References 23 publications

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“…Based on the TCGA database, links between high ACE2 expression and a favourable prognosis in clear cell renal cell carcinomas [ 7 ], and in colorectal carcinomas [ 8 ] have been described. Again, concordant with our findings, Nair et al [ 25 ] described a tendency towards poor patient prognosis in cancers with high ACE2 expression levels in an analysis of RNA expression data from a set of 2730 breast cancer patients, enriched for HER2 positive cases. Suggested mechanisms, by which elevated or decreased ACE2 protein levels could facilitate cancer progression, include stimulation of tumour angiogenesis [ 26 ] and inhibition of immune cell infiltration [ 27 ].…”

Section: Discussionsupporting

confidence: 92%

Angiotensin-Converting Enzyme 2 Protein Is Overexpressed in a Wide Range of Human Tumour Types: A Systematic Tissue Microarray Study on >15,000 Tumours

et al. 2021

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Angiotensin-converting enzyme 2 (ACE2) is a regulator in the renin-angiotensin system. ACE2 expression was analysed immunohistochemically in 15,306 samples from 119 tumour types and in 608 samples of 76 normal tissue types. In normal tissue, ACE2 was most abundant in testis and corpus luteum, kidney, small intestine and capillaries of selected organs. At least an occasional weak ACE2 positivity of tumour cells was seen in 83 of 119 (70%) tumour types. ACE2 tumour cell positivity was particularly frequent in papillary (94%) and clear cell (86%) renal cell carcinoma, colorectal adenocarcinoma (81%), mucinous ovarian cancer (61%), cholangiocarcinoma (58%), hepatocellular carcinoma (56%), and in adenocarcinomas of the stomach (47%), pancreas (42%), and the lung (35%). ACE2-positive capillaries were found in 409/12,644 (3%) of analysable tumours, most frequently in tumours with endocrine/neuroendocrine activity. Presence of ACE2-positive capillaries was linked to low stage in papillary thyroid cancer and low grade in neuroendocrine neoplasms. In conclusion, ACE2 expression can occur both in tumour cells and tumour-associated capillaries in a broad variety of different tumour types at highly variable frequencies.

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Section: Discussionsupporting

confidence: 92%

Angiotensin-Converting Enzyme 2 Protein Is Overexpressed in a Wide Range of Human Tumour Types: A Systematic Tissue Microarray Study on >15,000 Tumours

et al. 2021

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“…Although we cannot formally rule out the involvement of chromatin DNA and its sensors, cGAS and STING, in activating the senescence response induced by cell fusion, RIG-I-MAVS must play an essential role, because knockdown of MAVS or RIG-I, but ACE2 is abundantly expressed on not only human lung and small intestine epithelial cells but also vascular endothelial cells, arterial smooth muscle cells, cardiomyocytes, cardiofibroblasts, and coronary endothelial cells 33,34 . In addition, elevated expression of ACE2 has been observed across multiple tumour types [35][36][37] .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure

Wan¹,

Li²,

Huang³

et al. 2022

Preprint

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an important health threat. Syncytial formation by infected cells mediated by the SARS-CoV-2 spike protein (SARS-2-S) is a hallmark of COVID-19-associated pathology. Although SARS-CoV-2 infection evokes cellular senescence, as in other viruses, the direct link between SARS-2-S-induced syncytia with senescence in the absence of viral infection and their senescence fate determinants remain unknown. Here, we show that syncytia formed by cells expressing exogenously delivered SARS-2-S exhibited a senescence-like phenotype in vitro and that SARS-2-S mRNA induced senescence phenotype in vivo. Extracellular vesicles (EVs) containing SARS-2-S also induced senescent syncytium formation independent of the de novo synthesis of SARS-2-S. Mechanistically, we show that the accumulation of endogenous dsRNA, partially that whose formation is induced by activation of the unfolded protein response (UPR), in SARS-2-S syncytia triggers RIG-I-MAVS signalling to drive the TNF-α-dependent survival and senescence fate of SARS-2-S syncytia. Our findings suggest that the fusogenic ability of SARS-2-S might contribute to the side effects of particular COVID-19 vaccines or perhaps long COVID-19 syndrome and provide insight into how these effects can be prevented.

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“…Elevated levels of CA 15-3 or CEA have been shown to be associated with poor disease-free and overall survival [3,10,11]. The prognostic role of angiotensinconverting enzyme 2 (ACE2) has been described, elevated levels of which correlated with a decrease in disease-free survival [12]. Prognostic indicators based on inflammation are mentioned in the literature, including the ratio of neutrophils to lymphocytes, the ratio of lymphocytes to monocytes, the ratio of platelets to lymphocytes, and the ratio of C-reactive protein/albumin [10,13,14].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Salivary Biochemical Indicators in Primary Resectable Breast Cancer

Bel’skaya

Sarf

2022

Metabolites

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Despite the fact that breast cancer was detected in the early stages, the prognosis was not always favorable. In this paper, we examined the impact of clinical and pathological characteristics of patients and the composition of saliva before treatment on overall survival and the risk of recurrence of primary resectable breast cancer. The study included 355 patients of the Omsk Clinical Oncology Center with a diagnosis of primary resectable breast cancer (T1-3N0-1M0). Saliva was analyzed for 42 biochemical indicators before the start of treatment. We have identified two biochemical indicators of saliva that can act as prognostic markers: alkaline phosphatase (ALP) and diene conjugates (DC). Favorable prognostic factors were ALP activity above 71.7 U/L and DC level above 3.93 c.u. Additional accounting for aspartate aminotransferase (AST) activity allows for forming a group with a favorable prognosis, for which the relative risk is reduced by more than 11 times (HR = 11.49, 95% CI 1.43–88.99, p = 0.01591). Salivary AST activity has no independent prognostic value. Multivariate analysis showed that tumor size, lymph nodes metastasis status, malignancy grade, tumor HER2 status, and salivary ALP activity were independent predictors. It was shown that the risk of recurrence decreased with menopause and increased with an increase in the size of the primary tumor and lymph node involvement. Significant risk factors for recurrence were salivary ALP activity below 71.7 U/L and DC levels below 3.93 c.u. before treatment. Thus, the assessment of biochemical indicators of saliva before treatment can provide prognostic information comparable in importance to the clinicopathological characteristics of the tumor and can be used to identify a risk group for recurrence in primary resectable breast cancer.

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High expression of ACE2 in HER2 subtype of breast cancer is a marker of poor prognosis

Cited by 11 publications

References 23 publications

Angiotensin-Converting Enzyme 2 Protein Is Overexpressed in a Wide Range of Human Tumour Types: A Systematic Tissue Microarray Study on >15,000 Tumours

Angiotensin-Converting Enzyme 2 Protein Is Overexpressed in a Wide Range of Human Tumour Types: A Systematic Tissue Microarray Study on >15,000 Tumours

SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure

Prognostic Value of Salivary Biochemical Indicators in Primary Resectable Breast Cancer

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