Proteomics: A panel of seven serum biomarkers as a promising diagnostic tool for breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22019-e22019
Author(s):  
R. Lastra ◽  
A. Monasterio ◽  
I. Alvarez-Busto ◽  
J. Mayordomo ◽  
J. Algorta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Serum Proteins ◽  
Simultaneous Detection ◽  
Serum Biomarkers ◽  
Protein Chip ◽  
Differentially Expressed ◽  
Clinical Validation ◽  
Serum Samples ◽  
Screening Programs ◽  
Healthy Women

e22019 Background: Conventionals serum biomarkets have a low sensibility in breast cancer diagnosis. Proteomic is a promising tool to identify new proteins profiles to be used in screening and early diagnosed. Methods: 1)Biomarker identification: Serum proteins from 114 women were separated and analysed by bidimensional gel electrophoresis; data from 72 patients (p) were compared with those from 42 control women to search for differentially expressed proteins. Several comparisons were performed between controls and p regarding clinical parameters such as histological type, tumour stage and lymph node affection (-/+). A total of 53 spots were found to be differentially expressed and identified by mass spectrometry (MS) as potential breast cancer biomarkers.2) Protein Chip development: A Protein Chip was developed with antibodies against six biomarkers and three control proteins (an antibody for the detection of a spiked control, for data normalization and two proteins as positive and negative controls). An antibody against CA15–3 antigen was also included as a reference breast tumour marker to be compared with our biomarker panel. 3) Clinical validation of the Protein Chip: A clinical validation study was carried out with 75 healthy women and 125 breast cancer p. After multivariate statistical analysis of the biomarker data, CA15–3 was discarded due to its low significance while a panel of 5 biomarkers was obtained as the best predictive model to discriminate p from healthy subjects. Results: 53 diferentially expressed proteins have been identified as potential breast cancer serum biomarkers after analysing 114 serum samples by 2DE Technology. A Protein Chip has been developed for the simultaneous detection of five serum biomarkers and three control proteins. After clinical validation with 200 p and healthy women, the sensitivity of the Protein Chip to detect breast cancer was 95% and its specificity was 27%. Conclusions: The high sensitivity of the Protein Chip suggests that it could be a valid tool to complement mammography (sensitivity < 80%) in breast cancer screening programs, specially when its sensitivity tends to decrease, as it happens in young women and dense breast cases. Larger clinical validation trials are being developed. This work is supported by INDAS BIOTECH. No significant financial relationships to disclose.

PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC

2021 ◽  
pp. 1-9
Author(s):  
Parvaneh Yazdanpanah ◽  
Ali Alavianmehr ◽  
Abbas Ghaderi ◽  
Ahmad Monabati ◽  
Mehdi Montazer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Serum Levels ◽  
Tumor Stage ◽  
Serum Samples ◽  
Healthy Women ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Tnbc Subtype ◽  
Cell Death Protein

BACKGROUND: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. OBJECTIVES: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). METHODS: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. RESULTS: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. CONCLUSION: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.

scholarly journals Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9753
Author(s):  
Chengcheng Tu ◽  
Feng Tao ◽  
Ying Qin ◽  
Mingzhu Wu ◽  
Ji Cheng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Lipid Metabolism ◽  
Pregnant Women ◽  
Serum Proteins ◽  
Late Onset ◽  
Differentially Expressed ◽  
Coagulation Cascade ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Bioinformatics Analyses

Background Preeclampsia remains a serious disorder that puts at risk the lives of perinatal mothers and infants worldwide. This study assessed potential pathogenic mechanisms underlying preeclampsia by investigating differentially expressed proteins (DEPs) in the serum of patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) compared with healthy pregnant women. Methods Blood samples were collected from four women with EOPE, four women with LOPE, and eight women with normal pregnancies, with four women providing control samples for each preeclampsia group. Serum proteins were identified by isobaric tags for relative and absolute quantitation combined with liquid chromatography–tandem mass spectrometry. Serum proteins with differences in their levels compared with control groups of at least 1.2 fold-changes and that were also statistically significantly different between the groups at P < 0.05 were further analyzed. Bioinformatics analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses, were used to determine the key proteins and signaling pathways associated with the development of PE and to determine those DEPs that differed between women with EOPE and those with LOPE. Key protein identified by mass spectrometry was verified by enzyme linked immunosorbent assay (ELISA). Results Compared with serum samples from healthy pregnant women, those from women with EOPE displayed 70 proteins that were differentially expressed with significance. Among them, 51 proteins were significantly upregulated and 19 proteins were significantly downregulated. In serum samples from women with LOPE, 24 DEPs were identified , with 10 proteins significantly upregulated and 14 proteins significantly downregulated compared with healthy pregnant women. Bioinformatics analyses indicated that DEPs in both the EOPE and LOPE groups were associated with abnormalities in the activation of the coagulation cascade and complement system as well as with lipid metabolism. In addition, 19 DEPs in the EOPE group were closely related to placental development or invasion of tumor cells. Downregulationof pregnancy-specific beta-1-glycoprotein 9 (PSG9) in the LOPE group was confirmed by ELISA. Conclusion The pathogenesis of EOPE and LOPE appeared to be associated with coagulation cascade activation, lipid metabolism, and complement activation. However, the pathogenesis of EOPE also involved processes associated with greater placental injury. This study provided several new proteins in the serum which may be valuable for clinical diagnosis of EOPE and LOPE, and offered potential mechanisms underpinning the development of these disorders.

Use of surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) to detect breast cancer markers in serum

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22133-e22133
Author(s):  
D. Boehm ◽  
A. Lebrecht ◽  
R. Schwirz ◽  
K. Keller ◽  
M. Schmidt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Protein Profiling ◽  
Breast Cancer Patients ◽  
Screening Programs ◽  
Healthy Women ◽  
Metastatic Relapse ◽  
Protein Chips ◽  
Detect Breast Cancer ◽  
Tof Ms

e22133 Background: Breast cancer is one of the most frequent and deadly cancers worldwide. Although the survival of patients has increased over the last decades, many patients die from metastatic relapse. Progresses in screening or early diagnosis will improve survival of breast cancer. Breast cancer has never had any good serum tumor markers. Therefore, we developed and evaluated a proteomics approach to search for new biomarkers in serum of breast cancer patients. Methods: Blood samples of 50 women with breast cancer (CA) and 50 healthy women (CTRL), matched to the age, were drawn prior to surgery. We used SELDI-TOF-MS for protein profiling with three different active surfaces of the protein chips: cationic exchanger (CM-10), hydrophobic surface (H50) and a strong anion exchange surface (Q10) with different binding properties. Data were analyzed by multivariate statistical techniques and artificial neural networks. Results: SELDI-TOF- MS could discriminate between serum of breast cancer patients and healthy women. We could generate a statistic significant (p<0.001) panel with 15 biomarkers resulting of multiple peaks with different molecular weights. The diagnostic pattern could differentiate CA from CRTL with specificity of 77% and sensitivity of 85% in serum. Conclusions: In this study we could exemplify SELDI-TOF-MS as a potential screening method to detect breast cancer patients by serum analysis. The protein chip technology could greatly facilitate the discovery of new and better biomarkers in breast cancer patients. This promising approach provides a high sensitivity and specificity by a less invasive method similar to mammography that is used in screening programs. No significant financial relationships to disclose.

Use of serum biomarkers to differentiate benign breast lesions from invasive breast cancer in women with a BI-RADS 3 or 4.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 20-20
Author(s):  
Meredith C. Henderson ◽  
Michael Silver ◽  
Susan Yeh ◽  
Christa Corn ◽  
Sherri Borman ◽  
...  
Keyword(s):  
Breast Imaging ◽  
Clinical Decision Making ◽  
Serum Proteins ◽  
Clinical Performance ◽  
Imaging Techniques ◽  
High Sensitivity ◽  
Serum Biomarkers ◽  
Serum Samples ◽  
Meso Scale Discovery ◽  
Multiple Imaging

20 Background: The Provista Biomarker Assay (PBA) combines multiple serum biomarkers, measured at high sensitivity, in order to determine the likelihood of an invasive breast tumor at the time of testing. PBA, when paired with traditional breast imaging technologies, provides a biochemical tool that can help guide additional imaging or biopsy decisions. As part of our ongoing efforts to characterize clinical performance, we conducted a proof-of-concept study wherein PBA assay performance was tested in prospectively enrolled BI-RADS 3 and 4 patients. Methods: To maximize performance and sensitivity, we utilized the Meso Scale Discovery ELISA-based system to analyze a randomized cohort of 350 prebiopsy serum samples from women under the age of 50. Enrollment in the trial required a BI-RADS 3 or 4 radiologic assessment utilizing multiple imaging modalities. Serum proteins and autoantibodies were measured for each patient and applied to a proprietary statistical algorithm. Results: We were able to obtain statistically significant differentiation using the Provista Biomarker Assay in women under age 50 who were characterized as BI-RADS 3 or 4. The majority of patients in the study were diagnosed with a benign breast lesion, consistent with prior studies. However, the data indicate that PBA, when used in combination with imaging techniques, more accurately informs clinical decision-making. Conclusions: The Provista Biomarker Assay provides a powerful tool for physicians to more accurately assess patients with a BI-RADS 3 or 4 classification. With more clinical evidence, the assay may translate into changes in clinical treatment decisions for women under the age of 50 with a BI-RADS 3 or 4 classification. Clinical trial information: NCT01839045.

scholarly journals Clinical and technical evaluation of ACS™BR serum assay of MUC1 gene-derived glycoprotein in breast cancer, and comparison with CA 15-3 assays

1997 ◽  
Vol 43 (4) ◽  
pp. 585-593 ◽  
Author(s):  
Gijsbert G Bon ◽  
Silvia von Mensdorff-Pouilly ◽  
Peter Kenemans ◽  
Gerard J van Kamp ◽  
Rob A Verstraeten ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Performance ◽  
Linear Regression Analysis ◽  
Breast Disease ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Disease ◽  
Healthy Women ◽  
Technical Evaluation

Abstract The mucin glycoprotein-detecting assay CA 15-3 is a valuable tool for monitoring the course of disease in breast cancer patients. Assays of CA 15-3 are based on the use of two MAbs to polymorphic epithelial mucin (PEM). We evaluated the technical and clinical performance of the Chiron ACSTM BR, an automated competitive chemiluminescence assay using a single MAb, B27.29, and compared the assay’s results with those of the Centocor CA 15-3 RIA, the Abbott IMx CA 15-3, and the Boehringer Mannheim Enzymun-Test CA 15-3. The study population consisted of 253 healthy women, 66 patients with benign breast disease, 168 breast cancer patients, and 76 patients with other carcinomas. In the technical evaluation, we assessed the precision and linearity on dilution of the ACS BR assay. Cutoff values (upper limits of values seen in healthy subjects) were determined for all four assays. Agreement between the assays was studied by linear regression analysis. The ACS BR assay gave within- and between-assay CVs of 2.2% and 3.9%, respectively. Three samples from healthy women gave discordant values by ACS BR and were not included in the calculations. All four assays exhibit a highly similar pattern when monitoring breast cancer disease; the closest agreement of values was obtained between ACS BR and Centocor CA 15-3. We conclude that the ACS BR assay is a fast and reliable immunoassay for measuring PEM in serum. Although it detects a slightly different epitope on the PEM molecule than is targeted in other assays, for cancer serum samples it agreed better with the original Centocor CA 15-3 assay than did the other two CA 15-3 assays tested.

scholarly journals Detection of Circulating Mammary Mucin (MUC1) and MUC1 Immune Complexes (MUC1-CIC) in Healthy Women

2001 ◽  
Vol 16 (2) ◽  
pp. 112-120 ◽  
Author(s):  
M.V. Croce ◽  
M.T. Isla-Larrain ◽  
M.R. Price ◽  
A. Segal-Eiras
Keyword(s):  
Breast Cancer ◽  
Pregnant Women ◽  
Immune Complexes ◽  
Epidemiological Evidence ◽  
Serum Samples ◽  
Lactating Women ◽  
Humoral Immune ◽  
Healthy Women ◽  
Pregnancy And Lactation ◽  
Study Population

There is convincing epidemiological evidence that multiparity provides protection against the development of breast cancer. In the present study we evaluated the levels of MUC1 and MUC1 circulating immune complexes (MUC1-CIC) in 135 serum samples obtained from healthy women. The study population included 13 women who had never been pregnant, 31 primiparous pregnant women, 36 multiparous pregnant women who had lactated, 5 multiparous pregnant women who had never lactated, 24 multiparous non-pregnant women who were lactating at the time of the study, 24 multiparous non-pregnant women who had lactated, and 2 multiparous non-pregnant women who had never lactated. The purpose of this work was to detect MUC1 variations during pregnancy and lactation as well as to study the possible induction of a humoral immune response against MUC1 in these conditions. We employed ELISA techniques to measure MUC1 (CASA test) and MUC1-CIC (IgM and IgG) using two anti-MUC1 monoclonal antibodies (MAbs): C595 and SM3. Statistical analysis was performed using the ANOVA test. The pooled results pertaining to pregnant versus non-pregnant women were compared and significant differences were observed in MUC1 and MUC1-CIC-IgM levels detected with both MAbs; the MUC1-CIC-IgG levels detected with C595 were increased in the pregnant group while the MUC1-CIC-IgG levels detected with SM3 did not show any significant differences. When the results were compared between lactating and non-lactating women, no significant differences were found. In conclusion, MUC1 and MUC1-CIC-IgM, detected with both MAbs, and MUC1-CIC-IgG levels detected with the MAb C595 are apparently induced by pregnancy.

scholarly journals Differentially expressed serum proteins in children with or without asthma as determined using isobaric tags for relative and absolute quantitation proteomics

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9971
Author(s):  
Ming Li ◽  
Mingzhu Wu ◽  
Ying Qin ◽  
Huaqing Liu ◽  
Chengcheng Tu ◽  
...  
Keyword(s):  
Childhood Asthma ◽  
Serum Proteins ◽  
Differentially Expressed ◽  
Biological Information ◽  
Noncommunicable Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Absolute Quantitation ◽  
Children With Asthma ◽  
Isobaric Tags

Background Although asthma is one of the most common chronic, noncommunicable diseases worldwide, the pathogenesis of childhood asthma is not yet clear. Genetic factors and environmental factors may lead to airway immune-inflammation responses and an imbalance of airway nerve regulation. The aim of the present study was to determine which serum proteins are differentially expressed between children with or without asthma and to ascertain the potential roles that these differentially expressed proteins (DEPs) may play in the pathogenesis of childhood asthma. Methods Serum samples derived from four children with asthma and four children without asthma were collected. The DEPs were identified by using isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Using biological information technology, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Cluster of Orthologous Groups of Proteins (COG) databases and analyses, we determined the biological processes associated with these DEPs. Key protein glucose-6-phosphate dehydrogenase (G6PD) was verified by enzyme linked immunosorbent assay (ELISA). Results We found 46 DEPs in serum samples of children with asthma vs. children without asthma. Among these DEPs, 12 proteins were significantly (>1.5 fold change) upregulated and 34 proteins were downregulated. The results of GO analyses showed that the DEPs were mainly involved in binding, the immune system, or responding to stimuli or were part of a cellular anatomical entity. In the KEGG signaling pathway analysis, most of the downregulated DEPs were associated with cardiomyopathy, phagosomes, viral infections, and regulation of the actin cytoskeleton. The results of a COG analysis showed that the DEPs were primarily involved in signal transduction mechanisms and posttranslational modifications. These DEPs were associated with and may play important roles in the immune response, the inflammatory response, extracellular matrix degradation, and the nervous system. The downregulated of G6PD in the asthma group was confirmed using ELISA experiment. Conclusion After bioinformatics analyses, we found numerous DEPs that may play important roles in the pathogenesis of childhood asthma. Those proteins may be novel biomarkers of childhood asthma and may provide new clues for the early clinical diagnosis and treatment of childhood asthma.

scholarly journals Laboratory Evaluation of a Point-of-Care Downward-Flow Assay for Simultaneous Detection of Antibodies to Treponema pallidum and Human Immunodeficiency Virus

2016 ◽  
Vol 54 (7) ◽  
pp. 1922-1924 ◽  
Author(s):  
S. Herbst de Cortina ◽  
C. C. Bristow ◽  
S. K. Vargas ◽  
D. G. Perez ◽  
K. A. Konda ◽  
...  
Keyword(s):  
Point Of Care ◽  
Simultaneous Detection ◽  
Treponema Pallidum ◽  
Antibody Detection ◽  
Laboratory Evaluation ◽  
Serum Samples ◽  
Downward Flow ◽  
Content Type ◽  
Screening Programs ◽  
Point Of Care Test

Combining the detection of syphilis and HIV antibodies into one point-of-care test integrates syphilis screening into already existing HIV screening programs, which may be particularly beneficial in settings such as antenatal care. Using the INSTI Multiplex downward-flow immunoassay, we tested 200 stored serum samples from high-risk patients enrolled in a longitudinal study on HIV infection and syphilis in Peruvian men who have sex with men and transgender women. This rapid assay detected HIV andTreponema pallidumserum antibodies with sensitivities of 100% (95% confidence interval [CI], 95.9% to 100%) and 87.4% (95% CI, 81.4% to 92.0%), respectively, and specificities of 95.5% (95% CI, 89.9% to 98.5%) and 97.0% (95% CI, 84.2% to 99.9%), respectively (n= 200). The sensitivity for syphilis antibody detection was higher in patients with a rapid plasma reagin titer of ≥1:8 (97.3%) than in those with a titer of ≤1:4 (90%) or a nonreactive titer (66.7%).

scholarly journals Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel

2021 ◽  
Vol 15 (8) ◽  
pp. e0009714
Author(s):  
Amanda Ribeiro dos Santos ◽  
Aline Dionizio ◽  
Mileni da Silva Fernandes ◽  
Marília Afonso Rabelo Buzalaf ◽  
Beatriz Pereira ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oxygen Transport ◽  
Clinical Cure ◽  
Tissue Repair ◽  
Serum Proteins ◽  
Differentially Expressed ◽  
Signaling Proteins ◽  
Differentially Expressed Proteins ◽  
Serum Samples ◽  
Transport Pathways

Background Pulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification. Methodology/Principal findings This non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS. Conclusions/Significance Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.

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