Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer.

The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorphisms and biochemical recurrence and clinicopathological features of prostate cancer. The TIMP3 rs9619311, rs9862, and rs11547635 genetic polymorphisms were analyzed by real-time polymerase chain reaction to determine their genotypic distributions in 579 patients with prostate cancer. This study found that individuals with the TIMP3 rs9619311 TC or TC + CC genotypes have a significantly higher risk of biochemical recurrence of prostate cancer (p = 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade (p = 0.012) and grade group upgrade (p = 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage (p = 0.030) and Gleason total score upgrade (p = 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer.

Impact of Matrix Metalloproteinase-11 Gene Polymorphisms on Biochemical Recurrence and Clinicopathological Characteristics of Prostate Cancer.

Prostate cancer is among the most common malignant tumors worldwide. Matrix metalloproteinase (MMP)-11 is involved in extracellular matrix degradation and remodeling and plays an essential role in cancer development and metastasis. This study investigated the association of MMP-11 polymorphisms with the clinicopathological characteristics and biochemical recurrence of prostate cancer. Five single-nucleotide polymorphisms (SNPs) of the MMP-11 were analyzed in 578 patients with prostate cancer through real-time polymerase chain reaction analysis. A prostate-specific antigen level of >10 ng/mL, Gleason grade groups 4 + 5, advanced tumor stage, lymph node metastasis, invasion, and high-risk D'Amico classification were significantly associated with biochemical recurrence in the patients (p < 0.001). MMP-11 rs131451 "TC + CC" polymorphic variants were associated with advanced clinical stage (T stage; p = 0.007) and high-risk D'Amico classification (p = 0.015) in patients with biochemical recurrence. These findings demonstrate that MMP-11 polymorphisms were not associated with prostate cancer susceptibility; however, the rs131451 polymorphic variant was associated with late-stage tumors and high-risk D'Amico classification in prostate cancer patients with biochemical recurrence. Thus, the MMP-11 SNP rs131451 may contribute to the tumor development in prostate cancer patients with biochemical recurrence.

Urinary Concentration Correction Methods for Arsenic, Cadmium, and Mercury: a Systematic Review of Practice-Based Evidence.

BACKGROUND: Urinary biomonitoring is widely used to assess environmental chemical exposure; however, a critical gap exists in whether and how to correct for the physiological variation in water content of spot urine samples. OBJECTIVE: The aim of this systematic review is to summarize the available evidence comparing the performance of urinary concentration correction methods used to determine urinary levels of arsenic, cadmium, and mercury. METHODS: We searched PubMed/MEDLINE, Embase, LILIAC, Web of Science, and TOXNET up to Sept. 5, 2017 for articles evaluating urinary concentration correction methods (e.g., urine creatinine [U-Cre], specific gravity [U-SG], osmolality [U-Osm]) compared to 24-h or timed urine specimens for levels of arsenic, cadmium, and mercury. Data on study design, methods of urine collection, and the performance of selected correction methods were extracted. RESULTS: A total of 10 papers met the inclusion criteria. Two papers evaluated the performance of urinary concentration correction methods for arsenic, four for cadmium, three for mercury, and one for multiple metals. The median sample size for arsenic was 105, for cadmium 107, and for mercury 35. The studies were highly heterogeneous in population selection, urine collection, urine quality control, statistical comparison among selected correction methods, and presentation of the results. The median (range) of correlation coefficients comparing each corrected values with corresponding levels of timed urine specimens are 0.74 (0.17-0.92) for un-correction (n = 13), 0.82 (0.52-0.98) for U-Cre (n = 13), and 0.75 (0.28-0.98) (n = 12) for U-SG. CONCLUSION: Findings from limited evidence support that urine creatinine and urine-specific gravity corrections remain practical approaches to correct metal concentrations for urine dilution as compared to 24-h or 12-h urine samples. Further studies with larger sample sizes are needed to clarify this fundamental issue of environmental biomonitoring using spot urine samples in both general and priority populations.

Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gamma-amino-n-butyric acid in human urine.

A simple and sensitive liquid chromatographic method is described for the analysis of gamma-amino-n-butyric acid (GABA) in human urine. GABA is increased in the urine of cancer patients and could be used as a biomarker in the diagnosis and treatment of related patients. The method is based on derivatizing GABA with a fluorescent reagent (naproxen acyl chloride) for transforming the non-chromophoric GABA to a derivative with chromophoric and fluorophoric properties. The resulting derivative is highly responsive to a fluorimetric detector (lambda(ex)=230 nm, lambda(em)=350 nm). The lower quantitation of the method is attainable at 100 nM GABA with a detection limit about 10nM (S/N=3 with 20 microL injected). Application of the method to the analysis of GABA in the urine of patients with ovarian and uterine cancer was demonstrated.