Peptides Generated Ex Vivo from Serum Proteins by Tumor-Specific Exopeptidases Are Not Useful Biomarkers in Ovarian Cancer

Abstract Background: The serum peptidome may be a valuable source of diagnostic cancer biomarkers. Previous mass spectrometry (MS) studies have suggested that groups of related peptides discriminatory for different cancer types are generated ex vivo from abundant serum proteins by tumor-specific exopeptidases. We tested 2 complementary serum profiling strategies to see if similar peptides could be found that discriminate ovarian cancer from benign cases and healthy controls. Methods: We subjected identically collected and processed serum samples from healthy volunteers and patients to automated polypeptide extraction on octadecylsilane-coated magnetic beads and separately on ZipTips before MALDI-TOF MS profiling at 2 centers. The 2 platforms were compared and case control profiling data analyzed to find altered MS peak intensities. We tested models built from training datasets for both methods for their ability to classify a blinded test set. Results: Both profiling platforms had CVs of approximately 15% and could be applied for high-throughput analysis of clinical samples. The 2 methods generated overlapping peptide profiles, with some differences in peak intensity in different mass regions. In cross-validation, models from training data gave diagnostic accuracies up to 87% for discriminating malignant ovarian cancer from healthy controls and up to 81% for discriminating malignant from benign samples. Diagnostic accuracies up to 71% (malignant vs healthy) and up to 65% (malignant vs benign) were obtained when the models were validated on the blinded test set. Conclusions: For ovarian cancer, altered MALDI-TOF MS peptide profiles alone cannot be used for accurate diagnoses.

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Mass Spectrometric Screening of Ovarian Cancer with Serum Glycans

Disease Markers ◽

10.1155/2014/634289 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

Jae-Han Kim ◽

Chang Won Park ◽

Dalho Um ◽

Ki Hwang Baek ◽

Yohahn Jo ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Serum Proteins ◽

Ca 125 ◽

Healthy Controls ◽

Training Set ◽

Test Set ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Tof Ms

Changes of glycosylation pattern in serum proteins have been linked to various diseases including cancer, suggesting possible development of novel biomarkers based on the glycomic analysis. In this study, N-linked glycans from human serum were quantitatively profiled by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and compared between healthy controls and ovarian cancer patients. A training set consisting of 40 healthy controls and 40 ovarian cancer cases demonstrated an inverse correlation betweenPvalue of ANOVA and area under the curve (AUC) of each candidate biomarker peak from MALDI-TOF MS, providing standards for the classification. A multibiomarker panel composed of 15 MALDI-TOF MS peaks resulted in AUC of 0.89, 80~90% sensitivity, and 70~83% specificity in the training set. The performance of the biomarker panel was validated in a separate blind test set composed of 23 healthy controls and 37 ovarian cancer patients, leading to 81~84% sensitivity and 83% specificity with cut-off values determined by the training set. Sensitivity of CA-125, the most widely used ovarian cancer marker, was 74% in the training set and 78% in the test set, respectively. These results indicate that MALDI-TOF MS-mediated serum N-glycan analysis could provide critical information for the screening of ovarian cancer.

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Detection of Ovarian Cancer Using Samples Sourced from the Vaginal Microenvironment

10.1101/597740 ◽

2019 ◽

Author(s):

Melissa M. Galey ◽

Alexandria N. Young ◽

Valentina Z. Petukhova ◽

Mingxun Wang ◽

Jian Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Disease Progression ◽

Xenograft Model ◽

Screening Methods ◽

Maldi Tof Ms ◽

Analytical Technique ◽

Maldi Tof ◽

Specificity And Sensitivity ◽

Biological Mixtures ◽

Tof Ms

AbstractMass spectrometry (MS) offers high levels of specificity and sensitivity in clinical applications, and we have previously been able to demonstrate that matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS is capable of distinguishing two-component biological mixtures at low limits of detection. Ovarian cancer is notoriously difficult to detect due to the lack of any screening methods for early detection. By sampling a local microenvironment, such as the vaginal fluids, a MS based method is presented that was capable of monitoring disease progression from vaginally collected, local samples from tumor bearing mice. A murine xenograft model of high grade serous ovarian carcinoma (HGSOC) was used for this study and vaginal lavages were obtained from mice on a weekly basis throughout disease progression and subjected to our MALDI-TOF MS workflow followed by statistical analyses. Proteins in the 4-20 kDa region of the mass spectrum could consistently be measured to yield a fingerprint that correlated with disease progression over time. These fingerprints were found to be statistically stable across all mice with the protein fingerprint converging towards the end point of the study. MALDI-TOF MS serves as a unique analytical technique for measuring a sampled vaginal microenvironment in a specific and sensitive manner for the detection of HGSOC in a murine model.

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Serum Peptidomic Profile as a Novel Biomarker for Rheumatoid Arthritis

International Journal of Rheumatology ◽

10.1155/2020/6069484 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Abeer A. Abdelati ◽

Rehab A. Elnemr ◽

Noha S. Kandil ◽

Fatma I. Dwedar ◽

Rasha A. Ghazala

Keyword(s):

Rheumatoid Arthritis ◽

Profile Analysis ◽

Magnetic Bead ◽

Response To Treatment ◽

Healthy Controls ◽

Protein Biomarkers ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Flight Mass Spectrometry ◽

Tof Ms

Over the last decades, there has been an increasing need to discover new diagnostic RA biomarkers, other than the current serologic biomarkers, which can assist early diagnosis and response to treatment. The purpose of this study was to analyze the serum peptidomic profile in patients with rheumatoid arthritis (RA) by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The study included 35 patients with rheumatoid arthritis (RA), 35 patients with primary osteoarthritis (OA) as the disease control (DC), and 35 healthy controls (HC). All participants were subjected to serum peptidomic profile analysis using magnetic bead (MB) separation (MALDI-TOF-MS). The trial showed 113 peaks that discriminated RA from OA and 101 peaks that discriminated RA from HC. Moreover, 95 peaks were identified and discriminated OA from HC; 38 were significant (p<0.05) and 57 nonsignificant. The genetic algorithm (GA) model showed the best sensitivity and specificity in the three trials (RA versus HC, OA versus HC, and RA versus OA). The present data suggested that the peptidomic pattern is of value for differentiating individuals with RA from OA and healthy controls. We concluded that MALDI-TOF-MS combined with MB is an effective technique to identify novel serum protein biomarkers related to RA.

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MALDI–TOF MS Characterization, Genetic Diversity, and Antifungal Susceptibility of Trichosporon s pecies from Iranian Clinical Samples

Mycoses ◽

10.1111/myc.13306 ◽

2021 ◽

Author(s):

Fatemeh Ahangarkani ◽

Macit Ilkit ◽

Narges Vaseghi ◽

Nina Zahedi ◽

Kamyar Zomorodian ◽

...

Keyword(s):

Genetic Diversity ◽

Antifungal Susceptibility ◽

Clinical Samples ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Tof Ms

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Performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of ovarian cancer: a systematic review and meta-analysis

Journal of Ovarian Research ◽

10.1186/s13048-019-0605-2 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Kexin Li ◽

Yuqing Pei ◽

Yue Wu ◽

Yi Guo ◽

Wei Cui

Keyword(s):

Ovarian Cancer ◽

Meta Analysis ◽

Laser Desorption ◽

Laser Desorption Ionization ◽

Ionization Time ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Flight Mass Spectrometry ◽

Tof Ms ◽

Matrix Assisted Laser

Abstract Background To evaluate the diagnostic performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for ovarian cancer. Patients and methods A thorough research was conducted in PubMed, Web of Science and Embase (until November 2018) to identify studies evaluating the accuracy of MALDI-TOF-MS for ovarian cancer. Using Meta-Disc1.4, Review Manager 5.3 and Stata 15.1 software to analyze the pooled results: sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals (CI). The summary receiver operating characteristic curves (SROC) and area under the curve (AUC) show the overall performance of MALDI-TOF-MS. Results Eighteen studies were included in the meta-analysis. Methodological quality analysis of the included studies showed that these articles were at low risk of bias and applicability concerns in total. Summary estimates of the diagnostic parameters were as follows: sensitivity, 0.77 (95% CI: 0.73–0.80); specificity, 0.72 (95% CI: 0.70–0.74), PLR, 2.80 (95% CI: 2.41–3.24); NLR, 0.30 (95% CI: 0.22–0.40) and DOR, 10.71 (95% CI: 7.81–14.68). And the AUC was 0.8336. Egger’s test showed no significant publication bias in this meta-analysis. Conclusion In conclusion, MALDI-TOF-MS shows a good ability for diagnosing ovarian cancer. Further evaluation and optimization of standardized procedures are necessary for complete relying on MALDI-TOF-MS to diagnose ovarian cancer.

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Evaluation of prostate cancer based on MALDI-TOF MS fingerprinting of nanoparticle-treated serum proteins/peptides

Talanta ◽

10.1016/j.talanta.2020.121331 ◽

2020 ◽

Vol 220 ◽

pp. 121331

Author(s):

Jiaojiao Sun ◽

Guopeng Yu ◽

Yi Yang ◽

Liang Qiao ◽

Bin Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Serum Proteins ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Tof Ms

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Development of MALDI-TOF mass spectrometry for the identification of lice isolated from farm animals

Parasite ◽

10.1051/parasite/2020026 ◽

2020 ◽

Vol 27 ◽

pp. 28 ◽

Cited By ~ 4

Author(s):

Basma Ouarti ◽

Maureen Laroche ◽

Souad Righi ◽

Mohamed Nadir Meguini ◽

Ahmed Benakhla ◽

...

Keyword(s):

Mass Spectrometry ◽

Rapid Identification ◽

Farm Animals ◽

Clinical Samples ◽

Blind Test ◽

Maldi Tof Ms ◽

Pediculus Humanus ◽

Maldi Tof ◽

Flight Mass Spectrometry ◽

Tof Ms

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is now routinely used for the rapid identification of microorganisms isolated from clinical samples and has been recently successfully applied to the identification of arthropods. In the present study, this proteomics tool was used to identify lice collected from livestock and poultry in Algeria. The MALDI-TOF MS spectra of 408 adult specimens were measured for 14 species, including Bovicola bovis, B. ovis, B. caprae, Haematopinus eurysternus, Linognathus africanus, L. vituli, Solenopotes capillatus, Menacanthus stramineus, Menopon gallinae, Chelopistes meleagridis, Goniocotes gallinae, Goniodes gigas, Lipeurus caponis and laboratory reared Pediculus humanus corporis. Good quality spectra were obtained for 305 samples. Spectral analysis revealed intra-species reproducibility and inter-species specificity that were consistent with the morphological classification. A blind test of 248 specimens was performed against the in-lab database upgraded with new spectra and validated using molecular tools. With identification percentages ranging from 76% to 100% alongside high identification scores (mean = 2.115), this study proposes MALDI-TOF MS as an effective tool for discriminating lice species.

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Identification of Differential N-Glycan Compositions in the Serum and Tissue of Colon Cancer Patients by Mass Spectrometry

Biology ◽

10.3390/biology10040343 ◽

2021 ◽

Vol 10 (4) ◽

pp. 343

Author(s):

Marcelo de M.A. Coura ◽

Eder A. Barbosa ◽

Guilherme D. Brand ◽

Carlos Bloch ◽

Joao B. de Sousa

Keyword(s):

Mass Spectrometry ◽

Colon Cancer ◽

Cancer Patients ◽

Total Serum ◽

Healthy Controls ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Cancer Tumor ◽

Glycan Profiling ◽

Tof Ms

Colorectal cancer (CRC) ranks second as the leading cause of cancer-related deaths worldwide. N-glycosylation is one of the most common posttranslational protein modifications. Therefore, we studied the total serum N-glycome (TSNG) of 13 colon cancer patients compared to healthy controls using MALDI-TOF/MS and LC-MS. N-glycosylation of cancer tumor samples from the same cohort were further quantified using a similar methodology. In total, 23 N-glycan compositions were down-regulated in the serum of colon cancer patients, mostly galactosylated forms whilst the mannose-rich HexNAc2Hex7, the fucosylated bi-antennary glycan HexNAc4Hex5Fuc1NeuAc2, and the tetra-antennary HexNAc6Hex7NeuAc3 were up-regulated in serum. Hierarchical clustering analysis of TSNG correctly singled out 85% of the patients from controls. Albeit heterogenous, N-glycosylation of tumor samples showed overrepresented oligomannosidic, bi-antennary hypogalactosylated, and branched compositions related to normal colonic tissue, in both MALDI-TOF/MS and LC-MS analysis. Moreover, compositions found upregulated in tumor tissue were mostly uncorrelated to compositions in serum of cancer patients. Mass spectrometry-based N-glycan profiling in serum shows potential in the discrimination of patients from healthy controls. However, the compositions profile in serum showed no parallel with N-glycans in tumor microenvironment, which suggests a different origin of compositions found in serum of cancer patients.

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