Salivary metabolomics with alternative decision tree-based machine learning methods for breast cancer discrimination

Takeshi Murata, Takako Yanagisawa, Toshiaki Kurihara, Miku Kaneko, Sana Ota, Ayame Enomoto, Masaru Tomita, Masahiro Sugimoto, Makoto Sunamura, Tetsu Hayashida, Yuko Kitagawa, Hiromitsu Jinno

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)


Purpose: The aim of this study is to explore new salivary biomarkers to discriminate breast cancer patients from healthy controls. Methods: Saliva samples were collected after 9 h fasting and were immediately stored at − 80 °C. Capillary electrophoresis and liquid chromatography with mass spectrometry were used to quantify hundreds of hydrophilic metabolites. Conventional statistical analyses and artificial intelligence-based methods were used to assess the discrimination abilities of the quantified metabolites. A multiple logistic regression (MLR) model and an alternative decision tree (ADTree)-based machine learning method were used. The generalization abilities of these mathematical models were validated in various computational tests, such as cross-validation and resampling methods. Results: One hundred sixty-six unstimulated saliva samples were collected from 101 patients with invasive carcinoma of the breast (IC), 23 patients with ductal carcinoma in situ (DCIS), and 42 healthy controls (C). Of the 260 quantified metabolites, polyamines were significantly elevated in the saliva of patients with breast cancer. Spermine showed the highest area under the receiver operating characteristic curves [0.766; 95% confidence interval (CI) 0.671–0.840, P ' 0.0001] to discriminate IC from C. In addition to spermine, polyamines and their acetylated forms were elevated in IC only. Two hundred each of two-fold, five-fold, and ten-fold cross-validation using different random values were conducted and the MLR model had slightly better accuracy. The ADTree with an ensemble approach showed higher accuracy (0.912; 95% CI 0.838–0.961, P ' 0.0001). These prediction models also included spermine as a predictive factor. Conclusions: These data indicated that combinations of salivary metabolomics with the ADTree-based machine learning methods show potential for non-invasive screening of breast cancer.

Original languageEnglish
Pages (from-to)591-601
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - 2019 Oct 1


  • Alternative decision tree
  • Biomarker
  • Breast cancer
  • Metabolomics
  • Polyamines
  • Saliva

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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