Elevated Plasma ACE2 and Shifted Ang 1-7/Ang II Ratios: A Novel Multi-Analyte Signature for Distinguishing Breast Cancer Patients from Healthy Controls—A Pilot Case-Control Study

Background: The renin-angiotensin system (RAS), traditionally known for its role in cardiovascular regulation, has also emerged as a key regulator of tumor progression and metastasis. Dysregulation of the RAS components has been implicated in breast cancer due to the significant presence of the RAS-related proteins in the breast tissue. This study aims to identify the dysregulated RAS components and investigate their potential as prognostic biomarkers. Methods: A pilot case-control study was carried out with 21 treatment-naïve breast cancer patients and 17 healthy controls. Plasma levels of Ang 1-7, Ang II, ACE2 and some cytokines were measured using LC-MS/MS and ELISA. ROC curves were used to assess changes in biomarker levels across the RAS components. Results: Breast cancer patients show significant dysregulation of the RAS components and Interleukin-10. The ratio of Ang 1-7/Ang II was reduced by over two-fold in breast cancer patients (p = 0.0442). While plasma ACE2 was significantly elevated in breast cancer patients (p = 0.0005), IL-10 was significantly suppressed (p = 0.0420). In exploratory logistic regression analysis, ACE2 showed potential as a classifier with improved discrimination when combined with Ang 1-7 and Ang II (AUC = 0.9396, accuracy = 92.59%). However, due to the small sample size and methodological limitations, these findings require further validation. Conclusions: Our hypothesis-generating study highlights the potential of RAS components as circulatory biomarkers, given their high accuracy in distinguishing breast cancer patients from healthy individuals. Despite promising results, external validation of this data in a larger, more diverse study cohort is recommended to generalize the findings.