Clinical Significance and Potential Molecular Mechanisms of Angiotensin-Converting Enzyme 2 in Colorectal Cancer

Abstract

Abstract Background Angiotensin-converting enzyme 2 (ACE2) has emerged as a focal point in cancer research due to its potential protective role in cancer progression, generating significant interest because of its negative correlation with oncogenic pathways and positive association with antitumor immune responses in various cancers. Objective The role of ACE2 in colorectal cancer (CRC) remains poorly understood, meriting further investigation. Methods This study employed mRNA and protein analyses to comprehensively examine ACE2 expression in CRC tissues. An internal sample validation and the integration of data from 3,101 samples collected across multiple research centers support our findings. We evaluated ACE2’s ability to distinguish between CRC and non-CRC cases using the area under the receiver operating characteristic curve (AUC). Additionally, we explored the associations of ACE2 protein expression with CRC pathologic type and PDL1 positivity and investigated potential mechanisms involving antiangiogenesis and immune response. Results Our study found a significant upregulation of ACE2 mRNA and protein expression in CRC tissues, which was substantiated by internal validation and data integration. ACE2 exhibited strong discriminatory capacity, with an AUC of 0.844, effectively distinguishing CRC from non-CRC cases. Furthermore, ACE2 protein expression closely correlated with CRC pathologic type and PDL1 positivity among patients. The implicated mechanisms include antiangiogenesis and immune response. Conclusion The protein expression of ACE2 shows a close correlation with pathologic type and PDL1 positivity among patients with CRC. The underlying molecular mechanisms of ACE2 may be related to antiangiogenesis and immune response.