Dataset Information

Multiplex determination of serological signatures in the sera of colorectal cancer patients using hydrogel biochips.

ABSTRACT: Colorectal cancer (CRC) is the third most common malignancy in industrialized countries. Despite the advances in diagnostics and development of new drugs, the 5-year survival remains only 60-65%. Our approach to early diagnostics of CRC is based on the determination of serological signatures with an array of hemispherical hydrogel cells containing immobilized proteins and oligosaccharides (glycochip). The compounds immobilized on the glycochip include tumor-associated glycans (SiaTn, Tn, TF, Le(C) , Le(Y) , SiaLe(A) , and Man?1-4GlcNAc?) and antibodies against human immunoglobulins IgG, IgA, and IgM. The glycochip detects antibodies against tumor-associated glycans in patients' sera. The simultaneous measurement of the levels of immunoglobulins enhances the diagnostic impact of the signatures. In this work, we found previously unreported increase in antibodies against oligosaccharide Man?1-4GlcNAc? in patients with CRC. In parallel with these experiments, we determined the levels of oncomarkers carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA 125, CA 15-3, human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) using another gel-based biochip with immobilized antibodies (oncochip) developed earlier in our laboratory. In total, 69 samples from healthy donors, 33 from patients with colorectal carcinoma, and 27 from patients with inflammatory bowel diseases were studied. The use of combined signatures of antiglycan antibodies and oncomarkers provides much better predictive value than the conventional measurement of oncomarkers CEA and CA 19-9. Positive predictive value of CRC diagnoses using together glycochip and oncochip reached 95% with the sensitivity and specificity 88% and 98%, respectively. Thus, the combination of antibody profiling with detection of conventional oncomarkers proved to be a promising tool in diagnostics of CRC.

SUBMITTER: Butvilovskaya VI

PROVIDER: S-EPMC4944861 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Multiplex determination of serological signatures in the sera of colorectal cancer patients using hydrogel biochips.

Butvilovskaya Veronika I VI Popletaeva Sofya B SB Chechetkin Vladimir R VR Zubtsova Zhanna I ZI Tsybulskaya Marya V MV Samokhina Larisa O LO Vinnitskii Leonid I LI Ragimov Aligeydar A AA Pozharitskaya Elena I EI Grigor Eva Galina A GA Meshalkina Natalya Y NY Golysheva Svetlana V SV Shilova Nadezhda V NV Bovin Nicolai V NV Zasedatelev Aleksander S AS Rubina Alla Y AY

Cancer medicine 20160319 7

Colorectal cancer (CRC) is the third most common malignancy in industrialized countries. Despite the advances in diagnostics and development of new drugs, the 5-year survival remains only 60-65%. Our approach to early diagnostics of CRC is based on the determination of serological signatures with an array of hemispherical hydrogel cells containing immobilized proteins and oligosaccharides (glycochip). The compounds immobilized on the glycochip include tumor-associated glycans (SiaTn, Tn, TF, Le( ...[more]

PMID: 26992329

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Project description:The challenging diagnosis and poor prognosis of cholangiocarcinoma require the determination of biomarkers. Autoantibodies could be used in the clinic as diagnostic markers for the early detection of tumours. By proteomic approaches, several autoantibodies were proposed as potential markers. We tried in this study, to perform a serological proteome analysis, using various antigenic substrates, including tumours and human liver.Sera from patients (n = 13) and healthy donors (n = 10) were probed on immunoblots performed using 2-dimensionally separated proteins from cholangiocarcinoma cell lines (CCLP1 and CCSW1), from the liver of healthy subject and interestingly, from tumour and adjacent non-tumour liver tissues from five patients with cholangiocarcinoma and tested with their corresponding serum. Spots of interest were identified using mass spectrometry and classified according gene ontology analysis.A comparison of the whole immunoblotting patterns given by cholangiocarcinoma sera against those obtained with normal control sera enabled the definition of 862 spots. Forty-five different proteins were further analysed, corresponding to (1) spots stained with more than four of 13 (30 %) sera tested with the CCLP1 or the CCSW1 cell line and with the normal liver, and (2) to spots immunoreactive with at least two of the five sera probed with their tumour and non-tumour counter-part of cholangiocarcinoma. Immunoreactive proteins with catalytic activity as molecular function were detected at rates of 93 and 64 % in liver from healthy subjects or cholangiocarcinoma non-tumour tissues respectively, compared to 43, 33, 33 % in tumour tissues, or CCSW1 and CCLP1 cell lines. A second pattern was represented by structural proteins with rates of 7 and 7 % in normal liver or non-tumour tissues compared to 14, 33 and 67 % in tumour tissue, CCSW1 or CCLP1 cell lines. Proteins with a binding function were detected at rates of 7 % in non-tumour tissue and 14 % in tumour tissue. Using the extracted tumour tissue, serotransferrin was targeted by all cholangiocarcinoma-related sera.Immunological patterns depended on the type of antigen substrate used; i.e. tumour versus non tumour specimens. Nevertheless, a combination of multiple autoantibodies tested with the most appropriate substrate might be more sensitive and specific for the diagnosis of cholangiocarcinoma.

Project description:Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of "relevant miRNAs", we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2-90.0), and 77% (CI 64.2-85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1-92.1), and 81% (65.0-90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4-99.1), and 100% (83.9-100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the potential to discriminate between PTB and LTBI, but also among the other categories.

Dataset Information

Multiplex determination of serological signatures in the sera of colorectal cancer patients using hydrogel biochips.

Publications

Multiplex determination of serological signatures in the sera of colorectal cancer patients using hydrogel biochips.

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