Urinary Polyamine Biomarker Panels with Machine-Learning Differentiated Colorectal Cancers, Benign Disease, and Healthy Controls

Abstract

Colorectal cancer (CRC) is one of the most daunting diseases due to its increasing worldwide prevalence, which requires imperative development of minimally or non-invasive screening tests. Urinary polyamines have been reported as potential markers to detect CRC, and an accurate pattern recognition to differentiate CRC with early stage cases from healthy controls are needed. Here, we utilized liquid chromatography triple quadrupole mass spectrometry to profile seven kinds of polyamines, such as spermine and spermidine with their acetylated forms. Urinary samples from 201 CRCs and 31 non-CRCs revealed the N1,N12-diacetylspermine showing the highest area under the receiver operating characteristic curve (AUC), 0.794 (the 95% confidence interval (CI): 0.704–0.885, p < 0.0001), to differentiate CRC from the benign and healthy controls. Overall, 59 samples were analyzed to evaluate the reproducibility of quantified concentrations, acquired by collecting three times on three days each from each healthy control. We confirmed the stability of the observed quantified values. A machine learning method using combinations of polyamines showed a higher AUC value of 0.961 (95% CI: 0.937–0.984, p < 0.0001). Computational validations confirmed the generalization ability of the models. Taken together, polyamines and a machine-learning method showed potential as a screening tool of CRC.

Metabolomics Biomarkers for Detection of Colorectal Neoplasms: A Systematic Review

“…Deng, Fang et al (2017) validated a biomarker panel that was suggested by H. Wang et al in 2014, and they found similarly high sensitivity [ 48 , 51 ]. N1, N12-Diacetylspermine was found to be an individual biomarker candidate by two different studies [ 47 , 56 ]. Performance indicators of urine and stool-based biomarker panels can be found in Figure 3 .…”

Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling

“…Notably, none of these biogenic amines were positively or negatively associated with genital inflammation. Arginine and its polyamine product N(1)-acetylspermine are indicative of rapidly proliferating cells [56] and positively correlated with Lactobacillus abundance and genital inflammation. Previously, arginine metabolism was previously highlighted as an emerging hallmark of cancer [33].…”

Polyamine metabolism and cancer: treatments, challenges and opportunities

“…N 1 , N 12 -diacetylspermine has also been observed in high concentrations in biofilm-associated, right-side colon cancers 60,61 . Finally, polyamines and polyamine metabolites measured in either urine or serum have shown potential as biomarkers for prostate, colon and pancreatic cancers 62–66 . Such analyses, combined with increasingly precise genomic signatures, may aid in the development of more personalized approaches to cancer diagnosis and treatment based on using polyamines as biomarkers.…”