RESUMO
The prevalence of microsatellite instability and deoxyribonucleic acid mismatch repair deficiency in colorectal adenocarcinoma (CRC) cases is higher in India compared to western populations. No major study on the molecular pathogenesis is currently available in the Indian population. We conducted a pilot study to explore the differences in molecular pathogenesis of microsatellite stable (MSS) and microsatellite unstable CRC from a tertiary care centre in Kerala, South India. Using Nanostring PanCancer panel assay in Stage II colorectal adenocarcinoma, tumour tissues (n = 11) were compared against normal colon tissues (n = 4). Differentially expressed (DE) genes were identified and super-imposed onto colon adenocarcinoma cohort of The Cancer Genome Atlas (TCGA) data (TCGA Colon Adenocarcinoma (TCGA COAD)), from the Genome Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource (TIMER) to compare the gene associations. Significant DE genes were 59 out of 730 (false discovery rate adj. p-value < 0.05), 18 of which had a fold-change |FC(log2)| ≥ 2. On superimposition to TCGA COAD, 33 genes were significant in both TCGA and current study. ETV4 was expressed significantly higher in MSS with no immune cell infiltration. Other significant DE genes with high FC(log2), unique to the study were INHBA, COL1A1, COL11A1, COMP, SFRP4 and SPP1, which were clustered in STRING network analysis and correlated with tumour-infiltrating immune cells in TIMER, suggesting a specific interaction pathway. The preliminary study suggests a distinct pathogenesis of MSS CRC involving ETV4 in the Indian population and warrants further clinically extensive and high-dimensional expression studies.
RESUMO
BACKGROUND: Statins are a major group of drugs that reduces LDL-C levels, which are proven to have other beneficial effects such as preventing coronary events. The objective of this study was to evaluate oxidative stress and select novel coronary artery disease risk factors among coronary artery disease patients on statins. METHODS: In this observational, cross-sectional study, we compared total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein B, lipoprotein (a), homocysteine, reduced glutathione, glutathione peroxidase, superoxide dismutase, ascorbic acid, malondialdehyde and oxidized LDL among male coronary artery disease patients on statin therapy (group 2, n = 151) with sex-matched, diabetic patients (group 3, n = 80) as well as healthy controls (group 1, n = 84). RESULTS: Total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were significantly lower among subjects of group 2 compared to other two groups. The novel risk factors studied did not differ significantly between groups, except for a higher homocysteine level among group 2 subjects compared to the other two groups. Elevated oxidative stress, indicated by lower reduced glutathione, glutathione peroxidase, and ascorbic acid as well as higher malondialdehyde and oxidized LDL was observed among group 2 subjects. Triglycerides, HDL-cholesterol, ascorbic acid and malondialdehyde were found to be independent predictors for coronary artery disease among this study population. CONCLUSIONS: Though coronary artery disease subjects had healthy lipid profile, oxidative stress, a recognized risk factor for coronary events, was still elevated among this patient group. Novel risk factors were not found to be major predictors for coronary artery disease among the study subjects.
