Analytical and Bioanalytical Chemistry

, Volume 408, Issue 20, pp 5407–5414

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue

  • Clint M. Alfaro
  • Alan K. Jarmusch
  • Valentina Pirro
  • Kevin S. Kerian
  • Timothy A. Masterson
  • Liang Cheng
  • R. Graham Cooks
Rapid Communication

DOI: 10.1007/s00216-016-9627-4

Cite this article as:
Alfaro, C.M., Jarmusch, A.K., Pirro, V. et al. Anal Bioanal Chem (2016) 408: 5407. doi:10.1007/s00216-016-9627-4

Abstract

Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1–5 cm3), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700–1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700–1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl] and 844 [PC 38:4 + Cl] for TS vs. m/z 788 [PS 36:1 − H] and 810 [PS 38:4 − H] for DESI), while m/z 885 ([PI 38:4 − H]) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed.

Graphical abstract

Touch spray-mass spectrometry used for lipid profiling of fresh human renal cell carcinoma. Left) Photograph of the touch spray probe pointed at the MS inlet. Right) Average mass spectra of healthy renal tissue (blue) and RCC (red)

Keywords

Touch spray ionization Desorption electrospray ionization Mass spectrometry Multivariate statistics Surgical tissue analysis Cancer 

Supplementary material

216_2016_9627_MOESM1_ESM.pdf (2.2 mb)
ESM 1(PDF 2287 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Clint M. Alfaro
    • 1
  • Alan K. Jarmusch
    • 1
  • Valentina Pirro
    • 1
  • Kevin S. Kerian
    • 1
  • Timothy A. Masterson
    • 2
  • Liang Cheng
    • 3
  • R. Graham Cooks
    • 1
  1. 1.Department of Chemistry, Center for Analytical Instrumentation Development and Purdue University Center for Cancer ResearchPurdue UniversityWest LafayetteUSA
  2. 2.Department of Urology, Indiana University School of MedicineIndiana University Melvin and Bren Simon Cancer CenterIndianapolisUSA
  3. 3.Department of Pathology and Laboratory Medicine, Indiana University School of MedicineIndiana University Melvin and Bren Simon Cancer CenterIndianapolisUSA

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