METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.
RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.
CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.
IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
METHODS: Plasma protein profiling was performed for HIV patients with CKD presented with negative/trace proteinuria (non-proteinuric) (n = 8) and their matched non-CKD controls, using two-dimensional gel electrophoresis (2DE); selected protein candidates were identified using mass spectrometry. Subsequently, altered plasma abundance of protein candidates were verified using Western blotting in HIV-infected subjects with non-proteinuric CKD (n = 8), proteinuric CKD (n = 5), and their matched non-CKD controls, as well as in HIV-uninfected subjects with impaired kidney function (n = 3) and their matched controls.
RESULTS: Analysis of 2DE found significantly altered abundance of five protein candidates between HIV-infected patients with non-proteinuric CKD and without CKD: alpha-1-microglobulin (A1M), serum albumin (ALB), zinc-alpha-2-glycoprotein (AZGP1), haptoglobin (HP), and retinol binding protein (RBP4). Western blotting showed an increased abundance of A1M and HP in HIV-infected patients with non-proteinuric CKD compared to their non-CKD controls, whereas A1M, AZGP1, and RBP4 were significantly increased in HIV-infected patients with proteinuric CKD compared to their non-CKD controls. Such pattern was not found in HIV-uninfected subjects with impaired kidney function.
CONCLUSION: The data suggests four proteins that may be used as biomarkers of CKD in HIV-infected patients. Further validation in a larger cohort of HIV-infected patients is necessary for assessing the clinical use of these proposed biomarkers for CKD.
METHODOLOGY: The patients were 487 non-diabetic Malay women who had an uncomplicated antenatal course and delivered healthy singleton babies at term. Cord blood and maternal post-partum venous blood samples were taken for assay of serum cholesterol and triglyceride concentrations using standard enzymatic methods.
RESULTS: Maternal total serum cholesterol concentrations (mean +/- SD; 7.5 +/- 2.5 mmol/L) were higher than in other reported series (range of published means 5.2-6.5 mmol/L) with a correspondingly low high-density lipoprotein (HDL): total cholesterol ratio. The mean cord blood total serum cholesterol (1.7 +/- 1.0 mmol/L) was consistent with previously reported population means (1.5-1.9 mmol/L) but there was a relatively high low-density lipoprotein (LDL)-cholesterol and depressed HDL: cholesterol ratio. Significant correlations between maternal and neonatal serum total (P = 0.038) and especially HDL-cholesterol (P < 0.001) were observed. Maternal and cord blood serum triglyceride levels were comparable to those in other series.
CONCLUSIONS: These cross-sectional data provide evidence that abnormal serum cholesterol profiles are found in pregnant Malay women and their neonates which may have implications for the prevalence of macrovascular disease in the Malay population.