Matrix-assisted laser desorption/ionisation (MALDI) TOF analysis identifies serum angiotensin II concentrations as a strong predictor of all-cause and breast cancer (BCa)-specific mortality following breast surgery

Francesco Boccardo, Alessandra Rubagotti, Pier Vitale Nuzzo, Francesca Argellati, Grazia Savarino, Paolo Romano, Gianluca Damonte, Mattia Rocco, Aldo Profumo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

MALDI-TOF MS was used to recognise serum peptidome profiles predictive of mortality in women affected by early BCa. Mortality was analysed based on signal profiling, and appropriate statistics were used. The results indicate that four signals were increased in deceased patients compared with living patients. Three of the four signals were individually associated with all-cause mortality, but only one having mass/charge ratio (m/z) 1,046.49 was associated with BCa-specific mortality and was the only peak to maintain an independent prognostic role after multivariate analysis. Two groups exhibiting different mortality probabilities were identified after clustering patients based on the expression of the four peptides, but m/z 1,046.49 was exclusively expressed in the cluster exhibiting the worst mortality outcome, thus confirming the crucial value of this peptide. The specific role of this peak was confirmed by competing risk analysis. MS findings were validated by ELISA analysis after demonstrating that m/z 1,046.49 structurally corresponded to Angiotensin II (ATII). In fact, mortality results obtained after arbitrarily dividing patients according to an ATII serum value of 255 pg/ml (which corresponds to the 66th percentile value) were approximately comparable to those previously demonstrated when the same patients were analysed according to the expression of signal m/z 1,046.49. Similarly, ATII levels were specifically correlated with BCa-related deaths after competing risk analysis. In conclusion, ATII levels were increased in women who exhibited worse mortality outcomes, reinforcing the evidence that this peptide potentially significantly affects the natural history of early BCa. Our findings also confirm that MALDI-TOF MS is an efficient screening tool to identify novel tumour markers and that MS findings can be rapidly validated through less complex techniques, such as ELISA. What's new? Peptide signals emerging from the serum of cancer patients offer a glimpse into tumor activity, and as a result they hold significant promise as cancer biomarkers. This study concentrated on the serum peptidome of women who underwent surgery for breast cancer and who were followed for decades thereafter. Using mass spectrometry and statistical analyses of patient mortality data, the authors identified a peak with a mass/charge ratio of 1046.49 that was consistent with the structure of angiotensin II and was strongly predictive of breast cancer-specific mortality. The findings were confirmed by an ELISA immunoassay specific for angiotensin II.

Original languageEnglish
Pages (from-to)2394-2402
Number of pages9
JournalInternational Journal of Cancer
Volume137
Issue number10
DOIs
Publication statusPublished - Nov 15 2015

Fingerprint

Angiotensin II
Breast
Lasers
Breast Neoplasms
Mortality
Serum
Enzyme-Linked Immunosorbent Assay
Tumor Biomarkers
Peptides
Protein Sorting Signals
Immunoassay
Cluster Analysis
Mass Spectrometry
Neoplasms
Multivariate Analysis

Keywords

  • angiotensin
  • biomarkers
  • breast cancer
  • MALDI-TOF MS
  • proteomics
  • serum profiling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Matrix-assisted laser desorption/ionisation (MALDI) TOF analysis identifies serum angiotensin II concentrations as a strong predictor of all-cause and breast cancer (BCa)-specific mortality following breast surgery. / Boccardo, Francesco; Rubagotti, Alessandra; Nuzzo, Pier Vitale; Argellati, Francesca; Savarino, Grazia; Romano, Paolo; Damonte, Gianluca; Rocco, Mattia; Profumo, Aldo.

In: International Journal of Cancer, Vol. 137, No. 10, 15.11.2015, p. 2394-2402.

Research output: Contribution to journalArticle

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abstract = "MALDI-TOF MS was used to recognise serum peptidome profiles predictive of mortality in women affected by early BCa. Mortality was analysed based on signal profiling, and appropriate statistics were used. The results indicate that four signals were increased in deceased patients compared with living patients. Three of the four signals were individually associated with all-cause mortality, but only one having mass/charge ratio (m/z) 1,046.49 was associated with BCa-specific mortality and was the only peak to maintain an independent prognostic role after multivariate analysis. Two groups exhibiting different mortality probabilities were identified after clustering patients based on the expression of the four peptides, but m/z 1,046.49 was exclusively expressed in the cluster exhibiting the worst mortality outcome, thus confirming the crucial value of this peptide. The specific role of this peak was confirmed by competing risk analysis. MS findings were validated by ELISA analysis after demonstrating that m/z 1,046.49 structurally corresponded to Angiotensin II (ATII). In fact, mortality results obtained after arbitrarily dividing patients according to an ATII serum value of 255 pg/ml (which corresponds to the 66th percentile value) were approximately comparable to those previously demonstrated when the same patients were analysed according to the expression of signal m/z 1,046.49. Similarly, ATII levels were specifically correlated with BCa-related deaths after competing risk analysis. In conclusion, ATII levels were increased in women who exhibited worse mortality outcomes, reinforcing the evidence that this peptide potentially significantly affects the natural history of early BCa. Our findings also confirm that MALDI-TOF MS is an efficient screening tool to identify novel tumour markers and that MS findings can be rapidly validated through less complex techniques, such as ELISA. What's new? Peptide signals emerging from the serum of cancer patients offer a glimpse into tumor activity, and as a result they hold significant promise as cancer biomarkers. This study concentrated on the serum peptidome of women who underwent surgery for breast cancer and who were followed for decades thereafter. Using mass spectrometry and statistical analyses of patient mortality data, the authors identified a peak with a mass/charge ratio of 1046.49 that was consistent with the structure of angiotensin II and was strongly predictive of breast cancer-specific mortality. The findings were confirmed by an ELISA immunoassay specific for angiotensin II.",
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AU - Nuzzo, Pier Vitale

AU - Argellati, Francesca

AU - Savarino, Grazia

AU - Romano, Paolo

AU - Damonte, Gianluca

AU - Rocco, Mattia

AU - Profumo, Aldo

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