Dataset Information

Potential of MALDI-TOF-based serum N-glycan analysis for the diagnosis and surveillance of breast cancer.

ABSTRACT: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based serum N-glycan analysis has gained acknowledgment for the diagnosis of breast cancer in recent years. In this study, the possibilities of expanding its application for breast cancer management and surveillance were discovered and evaluated. First, a novel MALDI-TOF platform, IDsys RT, was confirmed to be effective for breast cancer analysis, showing a maximum area under the curve of 0.91. Multiple N-glycan markers were identified and validated using this process, and they were found to be applicable for differentiating recurring breast cancer samples from healthy control or ordinary breast cancer samples. Recurrence samples were especially distinct from non-recurrence samples when N-glycan signatures were sampled in multiple time points and monitored via MALDI-TOF, throughout the therapy. These results suggested the feasibility of MALDI-TOF-based N-glycan analysis for tracking the molecular signatures of breast cancer and predicting recurrence.

SUBMITTER: Lee JW

PROVIDER: S-EPMC7644762 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potential of MALDI-TOF-based serum N-glycan analysis for the diagnosis and surveillance of breast cancer.

Lee Jong Won JW Lee Kyungsoo K Ahn Sei Hyun SH Son Byung Ho BH Ko Beom Seok BS Kim Hee Jeong HJ Chung Il Yong IY Kim Jisun J Lee Woochang W Ko Myung-Su MS Choi Soojeong S Chang Suhwan S Ko Chung Kon CK Lee Sae Byul SB Kim Dong-Chan DC

Scientific reports 20201105 1

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based serum N-glycan analysis has gained acknowledgment for the diagnosis of breast cancer in recent years. In this study, the possibilities of expanding its application for breast cancer management and surveillance were discovered and evaluated. First, a novel MALDI-TOF platform, IDsys RT, was confirmed to be effective for breast cancer analysis, showing a maximum area under the curve of 0.91. Multiple N ...[more]

PMID: 33154535

Similar Datasets

Project description:Triple-negative breast cancer (TNBC) is characterized with high diffusion, metastasis and recurrence. The early treatment and early diagnosis of TNBC are highly important for the survival of TNBC patients. Nevertheless, traditional methods for TNBC diagnosis, i.e. imaging examinations and tissue biopsy, cannot achieve early diagnosis, are invasive and associated with the risk of arousing tumor spreading. Herein, we developed colloidosomes-coupled matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantify free serum amino acids for the diagnosis of TNBC. Gold nanoparticles (AuNPs) were used to form water-in-oil colloidosomes and to encapsulate deproteinated serum for MALDI-TOF MS analysis. With small sample spot size (200-300 μm) and densely packed AuNPs monolayer, the dried sample spot from colloidosomes can facilitate MALDI-TOF MS analysis of small molecule metabolites with high sensitivity, high reproducibility and good quantification performance. We used the method to quantify free amino acids in human serum. A cohort of 30 TNBC patients, 30 breast lump patients and 30 healthy controls were recruited for the study. It was found that the concentrations of free amino acids in TNBC patients were significantly lower than that of heathy controls, and the concentrations were also significantly different from that of breast lump patients. Based on the quantities of serum free amino acids, we have built a machine learning-based classification model to differentiate TNBC patients from the controls, including healthy controls and breast lump patients, and the sensitivity, specificity and accuracy were 95%, 100% and 97%, respectively. The assay consumes less than 1 μL serum per analysis, and takes only minutes to analyze a sample. With the advantages of low cost, low sample consumption, high throughput in analysis and high accuracy in identification, the non-invasive liquid biopsy method is promising to be applied to clinical diagnosis of TNBC.

Project description:ObjectivesBacterial diagnosis of mycobacteria is often challenging because of the variability of the sensitivity and specificity of the assay used, and it can be expensive to perform accurately. Although matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has become the workhorse of clinical laboratories, the current MALDI methodology (which is based on cytosolic protein profiling) for mycobacteria is still challenging due to the number of steps involved (up to seven) and potential biosafety concerns. Knowing that mycobacteria produce surface-exposed species-specific lipids, we here hypothesized that the detection of those molecules could offer a rapid, reproducible and robust method for mycobacterial identification.MethodsWe evaluated the performance of an alternative methodology based on characterized species-specific lipid profiling of intact bacteria, without any sample preparation, by MALDI MS; it uses MALDI-time-of-flight (ToF) MS combined with a specific matrix (super-2,5-dihydroxybenzoic acid solubilized in an apolar solvent system) to analyse lipids of intact heat-inactivated mycobacteria. Cultured mycobacteria are heat-inactivated and loaded directly onto the MALDI target followed by addition of the matrix. Acquisition of the data is done in both positive and negative ion modes. Blinded studies were performed using 273 mycobacterial strains comprising both the Mycobacterium tuberculosis (Mtb) complex and non-tuberculous mycobacteria (NTMs) subcultured in Middlebrook 7H9 media supplemented with 10% OADC (oleic acid/dextrose/catalase) growth supplement and incubated for up to 2 weeks at 37°C.ResultsThe method we have developed is fast (<10 mins) and highly sensitive (<1000 bacteria required); 96.7% of the Mtb complex strains (204/211) were correctly assigned as MTB complex and 91.7% (22/24) NTM species were correctly assigned based only on intact bacteria species-specific lipid profiling by MALDI-ToF MS.ConclusionsIntact bacterial lipid profiling provides a biosafe and unique route for rapid and accurate mycobacterial identification.

Project description:BackgroundFor the purpose of epidemiological surveillance, the Hospital University Institute Méditerranée infection has implemented since 2013 a system named MIDaS, based on the systematic collection of routine activity materials, including MALDI-TOF spectra, and results. The objective of this paper is to present the pipeline we use for processing MALDI-TOF spectra during epidemiological surveillance in order to disclose proteinic cues that may suggest the existence of epidemic processes in complement of incidence surveillance. It is illustrated by the analysis of an alarm observed for Streptococcus pneumoniae.MethodsThe MALDI-TOF spectra analysis process looks for the existence of clusters of spectra characterized by a double time and proteinic close proximity. This process relies on several specific methods aiming at contrasting and clustering the spectra, presenting graphically the results for an easy epidemiological interpretation, and for determining the discriminating spectra peaks with their possible identification using reference databases.ResultsThe use of this pipeline in the case of an alarm issued for Streptococcus pneumoniae has made it possible to reveal a cluster of spectra with close proteinic and temporal distances, characterized by the presence of three discriminant peaks (5228.8, 5917.8, and 8974.3 m/z) and the absence of peak 4996.9 m/z. A further investigation on UniProt KB showed that peak 5228.8 is possibly an OxaA protein and that the absent peak may be a transposase.ConclusionThis example shows this pipeline may support a quasi-real time identification and characterization of clusters that provide essential information on a potentially epidemic situation. It brings valuable information for epidemiological sensemaking and for deciding on the continuation of the epidemiological investigation, in particular the involving of additional costly resources to confirm or invalidate the alarm.Clinical trials registrationNCT03626987.

Dataset Information

Potential of MALDI-TOF-based serum N-glycan analysis for the diagnosis and surveillance of breast cancer.

Publications

Potential of MALDI-TOF-based serum N-glycan analysis for the diagnosis and surveillance of breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets