1. Lipidome-based rapid diagnosis with machine learning for detection of TGF-β signalling activated area in head and neck cancer
- Author
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Kentaro Yoshimura, Hiroki Ishii, Daisuke Saigusa, Masao Saitoh, Kei Sakamoto, Keiji Miyazawa, Kei Ashizawa, Kaname Sakamoto, Hirotake Kasai, Keisuke Masuyama, and Sen Takeda
- Subjects
Cancer Research ,Machine learning ,computer.software_genre ,Diagnostic system ,Article ,Treatment failure ,Machine Learning ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Cell Line, Tumor ,medicine ,Humans ,Tgf β signalling ,030304 developmental biology ,0303 health sciences ,business.industry ,Genetic heterogeneity ,Head and neck cancer ,Oral cancer detection ,Translational research ,Lipidome ,medicine.disease ,Head and neck squamous-cell carcinoma ,Oncology ,Head and Neck Neoplasms ,Surgical oncology ,030220 oncology & carcinogenesis ,Lipidomics ,Artificial intelligence ,business ,computer ,Signal Transduction ,Transforming growth factor - Abstract
Background Several pro-oncogenic signals, including transforming growth factor beta (TGF-β) signalling from tumour microenvironment, generate intratumoural phenotypic heterogeneity and result in tumour progression and treatment failure. However, the precise diagnosis for tumour areas containing subclones with cytokine-induced malignant properties remains clinically challenging. Methods We established a rapid diagnostic system based on the combination of probe electrospray ionisation-mass spectrometry (PESI-MS) and machine learning without the aid of immunohistological and biochemical procedures to identify tumour areas with heterogeneous TGF-β signalling status in head and neck squamous cell carcinoma (HNSCC). A total of 240 and 90 mass spectra were obtained from TGF-β-unstimulated and -stimulated HNSCC cells, respectively, by PESI-MS and were used for the construction of a diagnostic system based on lipidome. Results This discriminant algorithm achieved 98.79% accuracy in discrimination of TGF-β1-stimulated cells from untreated cells. In clinical human HNSCC tissues, this approach achieved determination of tumour areas with activated TGF-β signalling as efficiently as a conventional histopathological assessment using phosphorylated-SMAD2 staining. Furthermore, several altered peaks on mass spectra were identified as phosphatidylcholine species in TGF-β-stimulated HNSCC cells. Conclusions This diagnostic system combined with PESI-MS and machine learning encourages us to clinically diagnose intratumoural phenotypic heterogeneity induced by TGF-β.
- Published
- 2020
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