Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data.

Autor:	Einhaus J; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany., Gaudilliere DK; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Hedou J; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Feyaerts D; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Ozawa MG; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA., Sato M; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Ganio EA; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Tsai AS; Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Stelzer IA; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Bruckman KC; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Amar JN; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Sabayev M; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Bonham TA; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Gillard J; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Diop M; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Cambriel A; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Mihalic ZN; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Valdez T; Division of Pediatrics, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA., Liu SY; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Division of Sleep Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA., Feirrera L; Department of Oral and Maxillofacial Surgery, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA., Lam DK; Department of Oral and Maxillofacial Surgery, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA., Sunwoo JB; Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA., Schürch CM; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Gaudilliere B; Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA., Han X; Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Nov 20; Vol. 26 (12), pp. 108486. Date of Electronic Publication: 2023 Nov 20 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.108486
Abstrakt:	Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4 + memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development. Competing Interests: C.M.S. is a scientific advisor to AstraZeneca plc, and is on the scientific advisory board of, has stock options in, and has received research funding from Enable Medicine, Inc. D.K.G., J.H., and B.G. are advisory board members at SurgeCare. (© 2023 The Author(s).)
Databáze:	MEDLINE
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