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 Masterson, Liang Cheng, R. Graham Cooks

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalAnalytical and Bioanalytical Chemistry
DOIs
StateAccepted/In press - May 20 2016

Fingerprint

Renal Cell Carcinoma
Ionization
Cells
Touch
Tissue
Kidney
Mass spectrometry
Mass Spectrometry
Principal Component Analysis
Principal component analysis
Discriminant Analysis
Discriminant analysis
Ions
Imaging techniques
Electrospray ionization
Desorption
Phospholipids
Blood
Negative ions
Air

Keywords

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

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue. / Alfaro, Clint M.; Jarmusch, Alan K.; Pirro, Valentina; Kerian, Kevin S.; Masterson, Timothy; Cheng, Liang; Cooks, R. Graham.

In: Analytical and Bioanalytical Chemistry, 20.05.2016, p. 1-8.

Research output: Contribution to journalArticle

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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. [Figure not available: see fulltext.]",
keywords = "Cancer, Desorption electrospray ionization, Mass spectrometry, Multivariate statistics, Surgical tissue analysis, Touch spray ionization",
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AU - Alfaro, Clint M.

AU - Jarmusch, Alan K.

AU - Pirro, Valentina

AU - Kerian, Kevin S.

AU - Masterson, Timothy

AU - Cheng, Liang

AU - Cooks, R. Graham

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N2 - 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. [Figure not available: see fulltext.]

AB - 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. [Figure not available: see fulltext.]

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KW - Desorption electrospray ionization

KW - Mass spectrometry

KW - Multivariate statistics

KW - Surgical tissue analysis

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