Abstract
Objectives The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. Materials and Methods NCBI's built-in statistical tool, GEO2R, was used to calculate Student's t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak's multiple comparison correction. Results Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT2 angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p < 0.01). AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT1 angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed. AGT, which encodes angiotensinogen, the angiotensin peptide precursor, was overexpressed in adenocarcinoma tissue. Conclusion The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.
Highlights
Lung cancer continues to be the leading cause of cancer deaths, and lung adenocarcinomas account for approximately 40% of all lung cancers (https://www.cancer.org/cancer/ lungcancer-non-smallcell/index)
To ascertain if the renin-angiotensin system (RAS) is altered in lung adenocarcinomas we evaluated the expression of 15 genes of the classical RAS (Figure 1) and extended components of the RAS as reported in a previous study [2]
Among the proteins that comprise the classical RAS, the gene for the AT1 subtype of the Angiotensin II (Ang II) receptor was the most highly expressed in normal lung tissue (Figures 2 and S1, and Table 2)
Summary
Lung cancer continues to be the leading cause of cancer deaths, and lung adenocarcinomas account for approximately 40% of all lung cancers (https://www.cancer.org/cancer/ lungcancer-non-smallcell/index (accessed 8/31/16)). To assess factors associated with lung adenocarcinomas, a gene expression study comparing normal lung tissue and lung tumor was undertaken using the HG-U133A Affymetrix gene chip [1]. While such associations do not establish causation, they characterize the underlying molecular marks or tumors and identify potential target sites for treatments. Angiotensin II (Ang II), the primary hormone of the RAS, promotes the proliferation of mouse fibroblast 3T3 cells (but not SV40 transformed 3T3 cells in culture) [3], DNA synthesis and proliferation of adrenal cortical cells in culture [4], and the hypertrophic and hyperplastic growth of vascular smooth muscle cells [5] Both myointimal hyperplasia and vascular smooth muscle DNA synthesis are increased in rats infused with Ang II [6].
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