Angiotensin‑converting enzyme 2 as an immune and prognostic biomarker in colorectal cancer

Angiotensin-converting enzyme 2 (ACE2) has been implicated as an oncogene in certain cancer types; however, there is a lack of analysis on the role of ACE2 in the predictive value for prognosis and immunotherapy response in various tumor types. This study used data from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER 2.0), cBioPortal, and ROC Plotter databases to analyze the expression, prognosis, and immune cell infiltration of ACE2 in various tumor types. Furthermore, we analyzed the correlation between the expression of ACE2 and clinicopathological characteristics in 119 pairs of colorectal cancer (CRC) tissues using immunohistochemistry analysis, and then conducted the in vitro experiments to verify the role of ACE2 in the migration and proliferation of CRC cells. We found that ACE2 was highly expressed in CRC tissues compared with adjacent normal tissues, and that CRC patients with high ACE2 expression levels showed poor survival. Additionally, combined bioinformatics and qRT-PCR analysis identified a strong negative correlation between ACE2 expression and natural killer cell infiltration in CRC. Meanwhile, ACE2 expression was significantly elevated in patients resistant to anti-CTLA-4 and anti-PD-L1 therapy and was linked to poor prognosis. In vitro experiments showed that silencing ACE2 inhibits the proliferation and invasion of CRC cells. These results highlight ACE2's involvement in CRC pathogenesis and cancer-immune interactions, positioning it as a promising prognostic and therapeutic biomarker in CRC.