Chemometric Analysis of Urinary Volatile Organic Compounds to Monitor the Efficacy of Pitavastatin Treatments on Mammary Tumor Progression over Time

Abstract

Volatile organic compounds (VOCs) in urine are potential biomarkers of breast cancer. Previously, our group has investigated breast cancer through analysis of VOCs in mouse urine and identified a panel of VOCs with the ability to monitor tumor progression. However, an unanswered question is whether VOCs can be exploited similarly to monitor the efficacy of antitumor treatments over time. Herein, subsets of tumor-bearing mice were treated with pitavastatin at high (8 mg/kg) and low (4 mg/kg) concentrations, and urine was analyzed through solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS). Previous investigations using X-ray and micro-CT analysis indicated pitavastatin administered at 8 mg/kg had a protective effect against mammary tumors, whereas 4 mg/kg treatments did not inhibit tumor-induced damage. VOCs from mice treated with pitavastatin were compared to the previously analyzed healthy controls and tumor-bearing mice using chemometric analyses, which revealed that mice treated with pitavastatin at high concentrations were significantly different than tumor-bearing untreated mice in the direction of healthy controls. Mice treated with low concentrations demonstrated significant differences relative to healthy controls and were reflective of tumor-bearing untreated mice. These results show that urinary VOCs can accurately and noninvasively predict the efficacy of pitavastatin treatments over time.

Extracting Information and Enhancing the Quality of Separation Data: A Review on Chemometrics-Assisted Analysis of Volatile, Soluble and Colloidal Samples

“…Podolskiy et al [62] analyzed the steroid profile of urine samples by GC-MS and analyzed data by LDA and a neural-network based discriminant analysis to evaluate the degradation of samples for anti-doping analyses. VOC analysis of urine samples was also used to evaluate the efficacy of antitumoral treatment of breast cancer by Grocki et al [63]. Yang et al [64], instead, analyzed urinary samples to evaluate candidate metabolites for the diagnosis of inherit metabolomic diseases.…”