ABSTRACT
BACKGROUND: Several pro-oncogenic signals, including transforming growth factor beta (TGF-ß) 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-ß signalling status in head and neck squamous cell carcinoma (HNSCC). A total of 240 and 90 mass spectra were obtained from TGF-ß-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-ß1-stimulated cells from untreated cells. In clinical human HNSCC tissues, this approach achieved determination of tumour areas with activated TGF-ß 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-ß-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-ß.
Subject(s)
Head and Neck Neoplasms/diagnosis , Lipidomics/methods , Machine Learning/standards , Transforming Growth Factor beta/metabolism , Cell Line, Tumor , Head and Neck Neoplasms/pathology , Humans , Signal TransductionABSTRACT
OBJECTIVES: Intraoperative identification of tumor margins is essential to achieving complete tumor resection. However, the process of intraoperative pathological diagnosis involves cumbersome procedures, such as preparation of cryosections and microscopic examination, thus requiring more than 30â¯min. Moreover, intraoperative diagnoses made by examining cryosections are occasionally inconsistent with postoperative diagnoses made by examining paraffin-embedded sections because the former are of poorer quality. We sought to establish a more rapid accurate method of intraoperative assessment. MATERIALS AND METHODS: A diagnostic algorithm of head and neck squamous cell carcinoma (HNSCC) using machine learning was constructed by mass spectra obtained from 15 non-cancerous and 19 HNSCC specimens by probe electrospray ionization mass spectrometry (PESI-MS). The clinical validity of this system was evaluated using intraoperative specimens of HNSCC and normal mucosa. RESULTS: A total of 114 and 141 mass spectra were acquired from non-cancerous and cancerous specimens, respectively, using both positive- and negative-ion modes of PESI-MS. These data were fed into partial least squares-logistic regression (PLS-LR) to discriminate tumor-specific spectral patterns. Leave-one-patient-out cross validation of this algorithm in positive- and negative-ion modes showed accuracies in HNSCC diagnosis of 90.48% and 95.35%, respectively. In intraoperative specimens of HNSCC, this algorithm precisely defined the borders of the cancerous regions; these corresponded with those determined by examining histologic sections. The procedure took approximately 5â¯min. CONCLUSION: This diagnostic system, based on machine learning, enables accurate discrimination of cancerous regions and has the potential to provide rapid intraoperative assessment of HNSCC margins.
Subject(s)
Algorithms , Carcinoma, Squamous Cell/diagnosis , Databases, Factual , Head and Neck Neoplasms/diagnosis , Machine Learning , Spectrometry, Mass, Electrospray Ionization/methods , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Intraoperative Period , Male , Middle Aged , Reproducibility of Results , Squamous Cell Carcinoma of Head and NeckABSTRACT
An 85-year-old man presented with a rare large aneurysm of the extracranial internal carotid artery (ICA) due to acute otitis media manifesting as Vernet's syndrome 2 weeks after the diagnosis of right acute otitis media. Angiography of the right extracranial ICA demonstrated an irregularly shaped large aneurysm with partial thrombosis. The aneurysm was treated by proximal ICA occlusion using endovascular coils. The ICA mycotic aneurysm was triggered by acute otitis media, and induced Vernet's syndrome as a result of direct compression to the jugular foramen. Extracranial ICA aneurysms due to focal infection should be considered in the differential diagnosis of lower cranial nerve palsy, although the incidence is thought to be very low.
