Abstract
Materials and Methods Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically. Results Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens. Conclusions Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of THOP, NLN, PRCP, and MAS1 gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.
Highlights
Seventeen genes (Figures 2–4, S1-S2) of the renin-angiotensin system (RAS) and related enzymes were selected for analysis in 148 laser capture microresected (LCM) and homogenized tissue samples of male patients with colorectal cancer (CRC) [83]
The changes in gene expression for each of the 17 RAS-related genes are described in Figures 2–4, S1-S2, and Table 1
The studies that focused on RAS components in CRC generally found a consistent correlation between RAS-related gene expression in CRC tissues with Angiotensin-Converting Enzyme (ACE), MasR, AT1R, and AT2R expression being altered in CRC primary and metastatic tissues [15, 27]
Summary
Colorectal cancer is the second leading cause of cancer-related deaths in the USA and it is the third most common cancer in males and in females [1]. It is the second leading cause of cancer in females and third leading cause in males, with over half of the cases occurring in developed regions [2]. While there has been a large focus on CRC prevention by screening modalities, much remains undiscovered regarding better treatment options for this often-fatal disease. The current gold standard modality for diagnostic screening and early intervention is colonoscopy. The prevalence of the disease remains high.
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