Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies

Rachel J. DeHoog, Jialing Zhang, Elizabeth Alore, John Q. Lin, Wendong Yu, Spencer Woody, Christopher Almendariz, Monica Lin, Anton F. Engelsman, Stan B. Sidhu, Robert Tibshirani, James Suliburk, Livia S. Eberlin

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.

Original languageEnglish (US)
Pages (from-to)21401-21408
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number43
DOIs
StatePublished - Oct 22 2019
Externally publishedYes

Keywords

  • Ambient mass spectrometry
  • Cancer diagnosis
  • Metabolic profiles
  • Molecular biomarkers
  • Thyroid nodule diagnosis

ASJC Scopus subject areas

  • General

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