Key result
Colorectal cancer progression is linked to marked upregulation of AT1, AT2, and MAS receptors.
Why the study?
The role of local renin-angiotensin system receptors in colorectal carcinogenesis and their expression changes throughout the adenoma-adenocarcinoma sequence were not fully understood.
Observational (n=161)
p-value: p=<0.001
RAS receptors are differentially regulated throughout the colorectal adenoma-carcinoma sequence, with loss of AT2 potentially contributing to aggressive behavior in advanced CRC.
Hypothesis-generating for RAS receptor modulation in CRC; leaves open any impact on clinical outcomes or therapy.
Background and Objective: Colorectal cancer (CRC) is a major health problem in developed countries.Adenomatous lesions in the large bowel are the main precursors of CRC and the adenoma-adenocarcinoma sequence still provides a solid model for research on carcinogenesis.The finding of local renin-angiotensin systems (RAS) has been crucial to understand the role of this peptidergic system in cancer and has opened new perspectives in the study of colorectal carcinogenetic processes.Methods: In this study we analyzed the immunohistochemical expression of three main RAS receptors (AT1, AT2 and MAS) in a large series of CRC samples (n=161), including uninvolved intestinal mucosa-adenoma-adenocarcinoma sequences from the same patients (n=50).Results: 1) AT1 and AT2 showed a biphasic expression pattern along the sequence.The expression significantly decreased in adenomas with respect to uninvolved mucosa but increased in CRCs.2) AT2 expression was lower in advanced CRCs with high local invasion (pT4), high stage (IV), high nodal (N2) and vascular invasion.3) MAS receptor was moderately expressed in the uninvolved mucosa and in adenomas.This expression increased very significantly in CRC tissues.Conclusions: These results suggest that: 1) RAS receptors are differentially regulated as the genetic and epigenetic alterations accumulate throughout the uninvolved mucosa-adenoma-CRC sequence.2) Loss of AT2 expression could contribute to the aggressive behavior of advanced CRC cells.
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Beitia et al. (2019) conducted an observational in Colorectal cancer (n=161). Renin-angiotensin system (RAS) receptors (AT1, AT2, MAS) expression vs. Uninvolved intestinal mucosa and adenomatous polyps was evaluated on Differences in immunohistochemical expression of AT1, AT2, and MAS receptors throughout the uninvolved mucosa-adenoma-adenocarcinoma sequence (p=<0.001). AT1 and AT2 receptors showed a biphasic expression pattern that decreased in adenomas and increased in colorectal cancers, while MAS receptor expression significantly increased in colorectal cancer tissues compared to uninvolved mucosa and adenomas (p<0.001).
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