scholarly journals The Thomsen-Friedenreich Antigen-Specific Antibody Signatures in Patients with Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Oleg Kurtenkov ◽  
Kaire Innos ◽  
Boris Sergejev ◽  
Kersti Klaamas
Keyword(s):  
Breast Cancer ◽  
Sialic Acid ◽  
Specific Antibody ◽  
Early Stage ◽  
Ammonium Thiocyanate ◽  
Sambucus Nigra ◽  
Serum Samples ◽  
Naturally Occurring ◽  
Diagnostic Potential ◽  
Antibody Isotypes

Alterations in the glycosylation of serum total immunoglobulins show these antibodies to have a diagnostic potential for cancer but the disease-related Abs to the tumor-associated antigens, including glycans, have still poorly been investigated in this respect. We analysed serum samples from patients with breast carcinoma (n = 196) and controls (n = 64) for the level of Thomsen-Friedenreich (TF) antigen-specific antibody isotypes, their sialylation, interrelationships, and the avidity by using ELISA with the synthetic TF-polyacrylamide conjugate as an antigen and the sialic acid-specificSambucus nigraagglutinin (SNA) and ammonium thiocyanate as a chaotrope. An increased sialylation of IgG and IgM, but a lower SNA reactivity of IgA TF antibodies, and a higher level and avidity of the TF-specific IgA were found in cancer patients. Other cancer-related signatures were the highly significant increase of the IgG/IgA ratio and the very low SNA/IgA index in cancer, including patients with an early stage of the disease. These changes showed a good diagnostic potential with about 80% accuracy. Thus, the level of naturally occurring anti-TF antigen antibodies, their sialylation profile, isotype distribution, and avidity displayed cancer-specific changes that could serve as novel noninvasive Ab-based biomarkers for early breast cancer.

scholarly journals Application of green synthesized WO3-poly glutamic acid nanobiocomposite for early stage biosensing of breast cancer using electrochemical approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hassan Nasrollahpour ◽  
Abdolhossein Naseri ◽  
Mohammad-Reza Rashidi ◽  
Balal Khalilzadeh
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Electrochemical Biosensor ◽  
Early Stage ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Electrochemical Approach ◽  
Her 2

AbstractBiopolymer films have drawn growing demand for their application in the point of care domain owing to their biocompatibility, eco-friendly, and eligibility for in vivo analyses. However, their poor conductivity restricts their sensitivity in diagnostics. For high-quality electrochemical biosensor monitoring, two vital factors to be greatly paid attention are the effective merge of amplification modifiers with transducing surface and the superior linking across the recognition interface. Here, we introduce an enzyme-free electrochemical biosensor based on electrosynthesized biocompatible WO3/poly glutamic acid nano-biocomposites to address the hardships specific to the analysis of circulating proteins clinical samples. In addition to its green synthesis route, the poor tendency of both components of the prepared nano-biocomposite to amine groups makes it excellent working in untreated biological samples with high contents of proteins. Several electrochemical and morphological investigations (SEM, EDX, and dot mapping) were fulfilled to gain a reliable and trustful standpoint of the framework. By using this nanobiosensor, the concentration of HER-2 was detectable as low as 1 fg mL−1 with a wide linear response between 1 ng mL−1 and 1 fg mL−1. Meanwhile, the protocol depicted ideal specificity, stability, and reproducibility for the detection of HER-2 protein in untreated serum samples of breast cancer patients.

scholarly journals Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Vivek Kumar ◽  
Sameer Gupta ◽  
Amrita Chaurasia ◽  
Manisha Sachan
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Ovarian Tissue ◽  
Characteristic Curve ◽  
Mirna Gene ◽  
Serum Samples ◽  
Cancer Management ◽  
Diagnostic Potential

BackgroundEpithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies among women worldwide. Early diagnosis of EOC could help in ovarian cancer management. MicroRNAs, a class of small non-coding RNA molecules, are known to be involved in post-transcriptional regulation of ~60% of human genes. Aberrantly expressed miRNAs associated with disease progression are confined in lipid or lipoprotein and secreted as extracellular miRNA in body fluid such as plasma, serum, and urine. MiRNAs are stably present in the circulation and recently have gained an importance to serve as a minimally invasive biomarker for early detection of epithelial ovarian cancer.MethodsGenome-wide methylation pattern of six EOC and two normal ovarian tissue samples revealed differential methylation regions of miRNA gene promoter through MeDIP-NGS sequencing. Based on log2FC and p-value, three hypomethylated miRNAs (miR-205, miR-200c, and miR-141) known to have a potential role in ovarian cancer progression were selected for expression analysis through qRT-PCR. The expression of selected miRNAs was analyzed in 115 tissue (85 EOC, 30 normal) and 65 matched serum (51 EOC and 14 normal) samples.ResultsAll three miRNAs (miR-205, miR-200c, and miR-141) showed significantly higher expression in both tissue and serum cohorts when compared with normal controls (p < 0.0001). The receiver operating characteristic curve analysis of miR-205, miR-200c, and miR-141 has area under the curve (AUC) values of 87.6 (p < 0.0001), 78.2 (p < 0.0001), and 86.0 (p < 0.0001), respectively; in advance-stage serum samples, however, ROC has AUC values of 88.1 (p < 0.0001), 78.9 (p < 0.0001), and 86.7 (p < 0.0001), respectively, in early-stage serum samples. The combined diagnostic potential of the three miRNAs in advance-stage serum samples and early-stage serum samples has AUC values of 95.9 (95% CI: 0.925–1.012; sensitivity = 96.6% and specificity = 80.0%) and 98.1 (95% CI: 0.941–1.021; sensitivity = 90.5% and specificity = 100%), respectively.ConclusionOur data correlate the epigenetic deregulation of the miRNA genes with their expression. In addition, the miRNA panel (miR-205 + miR-200c + miR-141) has a much higher AUC, sensitivity, and specificity to predict EOC at an early stage in both tissue and serum samples.

High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer.

1997 ◽  
Vol 15 (11) ◽  
pp. 3363-3367 ◽  
Author(s):  
M L Disis ◽  
S M Pupa ◽  
J R Gralow ◽  
R Dittadi ◽  
S Menard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Specific Antibody ◽  
Primary Tumor ◽  
Early Stage ◽  
High Titer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Specific Antibodies ◽  
Her 2

PURPOSE To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor. METHODS The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population. RESULTS The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of > or = 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (0%) normal controls (P < .01). The presence of antibodies to HER-2/neu also correlated to overexpression of HER-2/neu protein in the patient's primary tumor. Nine of 44 (20%) patients with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, whereas three of 63 (5%) patients with HER-2/neu-negative tumors had antibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%). CONCLUSION The presence of HER-2/neu antibodies in breast cancer patients and the correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu protein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic proteins as tumor markers, as well as the development and testing of vaccine strategies to induce and augment immunity to HER-2/neu for the treatment of breast cancer or prevention of recurrent disease.

Serum VEGF in patients (PTS) receiving bevacizimab (BEV) for early-stage breast cancer (ESBC): ICORG 08-10.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13520-e13520
Author(s):  
Norma O'Donovan ◽  
Alexandra Canonici ◽  
Imelda Parker ◽  
Tanya O'Shea ◽  
Brian Moulton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Serum Samples ◽  
Median Level ◽  
Her 2 ◽  
One Year ◽  
Endothelial Growth Factor ◽  
Time Point

e13520 Background: Approximately 30% of pts with ESBC develop metastasis despite apparently curative loco-regional therapy. Angiogenesis, partly mediated by vascular endothelial growth factor (VEGF), may promote metastases. BEV, an anti-VEGF monoclonal antibody which has some efficacy in metastatic BC is being studied as an adjuvant in ESBC, but there are no validated biomarkers, and the effect on VEGF levels in pts with ESBC is unknown. We studied VEGF serum concentration in ESBC receiving BEV. Methods: 106 pts with HER-2 negative ESBC were included in this study. Patients received 4 cycles of docetaxel (75 mg/m2) + cyclophosphamide (600 mg/m2) with BEV (15 mg/kg) once every three weeks for one year. Serum samples were collected prior to commencement of treatment, at 6 months and 12 months. The VEGF levels in serum samples were determined, at each time point, using a VEGF enzyme-linked immunosorbent assay (ELISA). Results: VEGF concentration was determined in serum samples from 65 patients. Three pts (5%) had no detectable VEGF at 0, 6 and 12 months. The median level of serum VEGF in the remaining 62 patients was 325.4 ± 244 pg/ml. These 62 patients showed a significant decrease in VEGF concentration after 6 and 12 months of treatment (median 9 ± 42.1 pg/ml, p<0.001 and 9 ± 43.9 pg/ml, p<0.001 respectively). However, no significant change in VEGF levels were observed at 12 months compared to 6 months (median 0 ± 60.3 pg/ml, p=0.704). Conclusions: Adjuvant therapy with chemotherapy and BEV is associated with a significant reduction in VEGF levels at 6 months.

scholarly journals Identification of biomarkers for periodontal disease using the immunoproteomics approach

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2327 ◽  
Author(s):  
Jesinda P. Kerishnan ◽  
Sani Mohammad ◽  
Muhamad Shaifunizam Alias ◽  
Alan Kang-Wai Mu ◽  
Rathna Devi Vaithilingam ◽  
...  
Keyword(s):  
Immune Response ◽  
Periodontal Disease ◽  
Early Stage ◽  
Disease Status ◽  
Study Patient ◽  
Oral Diseases ◽  
Serum Samples ◽  
Two Dimensional Gel Electrophoresis ◽  
Protein Levels ◽  
Diagnostic Potential

BackgroundPeriodontitis is one of the most common oral diseases associated with the host’s immune response against periodontopathogenic infection. Failure to accurately diagnose the stage of periodontitis has limited the ability to predict disease status. Therefore, we aimed to look for reliable diagnostic markers for detection or differentiation of early stage periodontitis using the immunoprotemic approach.MethodIn the present study, patient serum samples from four distinct stages of periodontitis (i.e., mild chronic, moderate chronic, severe chronic, and aggressive) and healthy controls were subjected to two-dimensional gel electrophoresis (2-DE), followed by silver staining. Notably, we consistently identified 14 protein clusters in the sera of patients and normal controls.ResultsOverall, we found that protein levels were comparable between patients and controls, with the exception of the clusters corresponding to A1AT, HP, IGKC and KNG1 (p < 0.05). In addition, the immunogenicity of these proteins was analysed via immunoblotting, which revealed differential profiles for periodontal disease and controls. For this reason, IgM obtained from severe chronic periodontitis (CP) sera could be employed as a suitable autoantibody for the detection of periodontitis.DiscussionTaken together, the present study suggests that differentially expressed host immune response proteins could be used as potential biomarkers for screening periodontitis. Future studies exploring the diagnostic potential of such factors are warranted.

scholarly journals Serum IgA1 shows increased levels of α 2,6-linked sialic acid in breast cancer

2019 ◽  
Vol 9 (2) ◽  
pp. 20180079 ◽  
Author(s):  
Hannah J. Lomax-Browne ◽  
Claire Robertson ◽  
Aristotelis Antonopoulos ◽  
Anthony J. C. Leathem ◽  
Stuart M. Haslam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sialic Acid ◽  
Tumour Size ◽  
Helix Pomatia ◽  
Immunohistochemical Analysis ◽  
Tumour Tissue ◽  
Serum Samples ◽  
Tissue Samples ◽  
Predictive Values ◽  
Iga1 Glycosylation

The lectin Helix pomatia agglutinin (HPA) recognizes altered glycosylation in solid cancers and the identification of HPA binding partners in tumour tissue and serum is an important aim. Among the many HPA binding proteins, IgA1 has been reported to be the most abundant in liver metastases. In this study, the glycosylation of IgA1 was evaluated using serum samples from patients with breast cancer (BCa) and the utility of IgA1 glycosylation as a biomarker was assessed. Detailed mass spectrometric structural analysis showed an increase in disialo-biantennary N- linked glycans on IgA1 from BCa patients ( p < 0.0001: non-core fucosylated; p = 0.0345: core fucosylated) and increased asialo-Thomsen–Friedenreich antigen (TF) and disialo-TF antigens in the O- linked glycan preparations from IgA1 of cancer patients compared with healthy control individuals. An increase in Sambucus nigra binding was observed, suggestive of increased α 2,6-linked sialic acid on IgA1 in BCa. Logistic regression analysis showed HPA binding to IgA1 and tumour size to be significant independent predictors of distant metastases ( χ 2 13.359; n = 114; p = 0.020) with positive and negative predictive values of 65.7% and 64.6%, respectively. Immunohistochemical analysis of tumour tissue samples showed IgA1 to be detectable in BCa tissue. This report provides a detailed analysis of serum IgA1 glycosylation in BCa and illustrates the potential utility of IgA1 glycosylation as a biomarker for BCa prognostication.

scholarly journals SIGNATURES OF ANTI-THOMSEN — FRIEDENREICH ANTIGEN ANTIBODY DIVERSITY IN COLON CANCER PATIENTS

2018 ◽  
Vol 40 (1) ◽  
pp. 48-58 ◽  
Author(s):  
O Krutenkov ◽  
M Bubina ◽  
K Klaamas
Keyword(s):  
Colon Cancer ◽  
Prognostic Value ◽  
Characteristic Curve ◽  
Ammonium Thiocyanate ◽  
Receiver Operator Characteristic Curve ◽  
Healthy Controls ◽  
Serum Samples ◽  
Antibody Diversity ◽  
Specific Antibodies ◽  
Diagnostic Potential

Aim: To determine whether the structural and functional diversities of naturally occurring antibodies to the Thomsen — Friedenreich (TF) antigen may be of diagnostic and prognostic value in colon cancer. Materials and Methods: Serum samples were taken from patients with colon cancer (n = 94) and healthy controls (n = 64). The level of TF-specific antibody isotypes and their sialylation were determined using ELISA and lectin-ELISA with synthetic TF-polyacrylamide conjugate as an antigen and a sialic acid-specific Sambucus nigra agglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope. The accuracy of diagnostics was evaluated using the receiver operator characteristic curve analysis and the survival analysis employing the Kaplan — Meier method. Results: Compared to healthy controls, patients with colon cancer exhibited a lower level of anti-TF IgG antibodies, significantly lower ratios of TF-specific IgG/IgM and IgG/IgA, an increased SNA reactivity of anti-TF antibodies, mostly on account of IgG, and a lower avidity of TF-specific antibodies, especially their SNA-reactive subset. An increased SNA reactivity of anti-TF IgG was observed already at the early stages of cancer (p = 0.0004). The decrease of the ratio of IgG/IgM and IgG/IgA showed a good accuracy of diagnostics with about 60% sensitivity at 90% specificity. A similar potential was found for the SNA binding/IgG level index. The high level of TF-specific IgA antibodies was associated with a lower survival rate (hazard ratio = 0.34). Conclusion: This is the first report ever on the colon cancer-related signatures of anti-TF antibody diversity which show diagnostic potential, including in early cancer, and prognostic value. The hypersialylation of TF-specific antibodies appeared to be a common phenomenon in cancer. The signatures may be used as non-invasive antibody-based markers for colon cancer.

scholarly journals Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Claudia Fredolini ◽  
Khyatiben V. Pathak ◽  
Luisa Paris ◽  
Kristina M. Chapple ◽  
Kristine A. Tsantilas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Detection ◽  
Early Stage ◽  
Multiple Reaction Monitoring ◽  
False Negative ◽  
Mammographic Screening ◽  
Breast Cancer Detection ◽  
Early Stage Breast Cancer ◽  
Integrin Subunit ◽  
Serum Samples

Abstract Background The lack of specificity and high degree of false positive and false negative rates when using mammographic screening for detecting early-stage breast cancer is a critical issue. Blood-based molecular assays that could be used in adjunct with mammography for increased specificity and sensitivity could have profound clinical impact. Our objective was to discover and independently verify a panel of candidate blood-based biomarkers that could identify the earliest stages of breast cancer and complement current mammographic screening approaches. Methods We used affinity hydrogel nanoparticles coupled with LC-MS/MS analysis to enrich and analyze low-abundance proteins in serum samples from 20 patients with invasive ductal carcinoma (IDC) breast cancer and 20 female control individuals with positive mammograms and benign pathology at biopsy. We compared these results to those obtained from five cohorts of individuals diagnosed with cancer in organs other than breast (ovarian, lung, prostate, and colon cancer, as well as melanoma) to establish IDC-specific protein signatures. Twenty-four IDC candidate biomarkers were then verified by multiple reaction monitoring (LC-MRM) in an independent validation cohort of 60 serum samples specifically including earliest-stage breast cancer and benign controls (19 early-stage (T1a) IDC and 41 controls). Results In our discovery set, 56 proteins were increased in the serum samples from IDC patients, and 32 of these proteins were specific to IDC. Verification of a subset of these proteins in an independent cohort of early-stage T1a breast cancer yielded a panel of 4 proteins, ITGA2B (integrin subunit alpha IIb), FLNA (Filamin A), RAP1A (Ras-associated protein-1A), and TLN-1 (Talin-1), which classified breast cancer patients with 100% sensitivity and 85% specificity (AUC of 0.93). Conclusions Using a nanoparticle-based protein enrichment technology, we identified and verified a highly specific and sensitive protein signature indicative of early-stage breast cancer with no false positives when assessing benign and inflammatory controls. These markers have been previously reported in cell-ECM interaction and tumor microenvironment biology. Further studies with larger cohorts are needed to evaluate whether this biomarker panel improves the positive predictive value of mammography for breast cancer detection.

scholarly journals Development and validation of a circulating microRNA panel for the early detection of breast cancer

2022 ◽  
Author(s):  
Ruiyang Zou ◽  
Sau Yeen Loke ◽  
Yew Chung Tang ◽  
Heng-Phon Too ◽  
Lihan Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Screening ◽  
Breast Cancer Screening ◽  
Early Stage ◽  
False Positive Rate ◽  
Area Under The Curve ◽  
Circulating Microrna ◽  
Serum Samples ◽  
Asian Populations ◽  
Multi Center Study

Abstract Background Mammography is widely used for breast cancer screening but suffers from a high false-positive rate. Here, we perform the largest comprehensive, multi-center study to date involving diverse ethnic groups, for the identification of circulating miRNAs for breast cancer screening. Methods This study had a discovery phase (n = 289) and two validation phases (n = 374 and n = 379). Quantitative PCR profiling of 324 miRNAs was performed on serum samples from breast cancer (all stages) and healthy subjects to identify miRNA biomarkers. Two-fold cross-validation was used for building and optimising breast cancer-associated miRNA panels. An optimal panel was validated in cohorts with Caucasian and Asian samples. Diagnostic ability was evaluated using area under the curve (AUC) analysis. Results The study identified and validated 30 miRNAs dysregulated in breast cancer. An optimised eight-miRNA panel showed consistent performance in all cohorts and was successfully validated with AUC, accuracy, sensitivity, and specificity of 0.915, 82.3%, 72.2% and 91.5%, respectively. The prediction model detected breast cancer in both Caucasian and Asian populations with AUCs ranging from 0.880 to 0.973, including pre-malignant lesions (stage 0; AUC of 0.831) and early-stage (stages I–II) cancers (AUC of 0.916). Conclusions Our panel can potentially be used for breast cancer screening, in conjunction with mammography.

scholarly journals Functional role of vitronectin in breast cancer

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242141
Author(s):  
Alakesh Bera ◽  
Madhan Subramanian ◽  
John Karaian ◽  
Michael Eklund ◽  
Surya Radhakrishnan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Functional Role ◽  
Cancer Survival ◽  
Early Stage ◽  
Critical Role ◽  
Breast Cancer Survival ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Serum Samples

Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection. Vitronectin, a glycoprotein that is abundantly found in serum, extracellular matrix, and bone, binds to integrin αvβ3, and promotes cell adhesion and migration. Current studies indicate that patients with amplified vitronectin levels have lower survival rates than patients without amplified vitronectin levels. In this study, we focused on the role of vitronectin in breast cancer survival and its functional role as a non-invasive biomarker for early stage and stage specific breast cancer detection. To confirm that the expression of vitronectin is amplified in breast cancer, a total of 240 serum samples (n = 240), 200 from breast cancer patients and 40 controls were analyzed using the Reverse Phase Protein Array (RPPA) technique. Of the 240 samples, 120 samples were of African American (AA) descent, while the other 120 were of White American (WA) descent. Data indicated that there were some possible racial disparities in vitronectin levels and, differences also seen in the recurrent patient samples. Next, we tried to uncover the underlying mechanism which plays a critical role in vitronectin expression. The cellular data from four different breast cancer cell lines- MCF7, MDA-MB-231, MDA-MB-468, and HCC1599 indicated that the PI3K/AKT axis is modulating the expression of vitronectin. We believe that vitronectin concentration levels are involved and connected to the metastasis of breast cancer in certain patients, specifically based on recurrence or ethnicity, which is detrimental for poor prognosis. Therefore, in this current study we showed that the serum vitronectin levels could be an early marker for the breast cancer survival and we also determine the cellular signaling factors which modulate the expression and concentration of vitronectin.

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