Tissue proteome profiling of preeclamptic placenta using recombinant antibody microarrays

Dexlin-Mellby, Linda; Sandström, Anna; Centlow, Magnus; Nygren, Sara; Hansson, Stefan R.; Borrebaeck, Carl; Wingren, Christer

doi:10.1002/prca.201000001

Cited by 22 publications

(17 citation statements)

References 86 publications

(163 reference statements)

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“…Notably, we showed herein that PDAC and pancreatitis could be specifically discriminated with high confidence. Furthermore, the observed signature(s) showed significant differences (only 4-11 analytes overlapped) with those observed for various inflammatory conditions, such as systemic lupus erythematosus, systemic sclerosis, preeclampsia, and Helicobacter pylori infection (25,32,33), as well as other types of cancers, such as breast cancer, gastric adenocarcinoma, and glioblastoma multiforme (17,18,22,25). Consequently, this further supported the current observation that we had defined a PDAC-associated signature rather than a general cancer or inflammatory signature.…”

Section: Discussionmentioning

confidence: 90%

Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer

Wingren

Sandström²,

Segersvärd³

et al. 2012

Cancer Research

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Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls (N). Serum biomarker signatures were derived from training cohorts and the predictive power was evaluated using independent test cohorts. The results identified serum portraits distinguishing pancreatic cancer from N [receiver operating characteristics area under the curve (AUC) of 0.95], chronic pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature discriminating pancreatic cancer from the combined group of N, chronic pancreatitis, and AIP was determined. This signature exhibited a high diagnostic potential (AUC of 0.88). In summary, we present the first prevalidated, multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may improve diagnosis and prevention in premalignant diseases and in screening of high-risk individuals. Cancer Res; 72(10);

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Section: Discussionmentioning

confidence: 90%

Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer

Wingren

Sandström²,

Segersvärd³

et al. 2012

Cancer Research

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100

111

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“…The probe source (format) has been found to display superior on-chip performances compared with conventional monoclonal and polyclonal antibodies [25,26]. The specific 13 antibodies used in this study were selected based on the criteria that they were tested to work well in microarray applications and directed against target antigens located in the cell surface membrane [19,27,28]. More specifically, we use recombinant scFv antibodies that have been designed for microarray applications by molecular design, thus displaying high-on chip performance.…”

Section: Methodsmentioning

confidence: 99%

Interfacing Antibody-Based Microarrays and Digital Holography Enables Label-Free Detection for Loss of Cell Volume

et al. 2015

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Background:We introduce the combination of digital holographic microscopy (DHM) and antibody microarrays as a powerful tool to measure morphological changes in specifically antibody-captured cells. The aim of the study was to develop DHM for analysis of cell death of etoposide-treated suspension cells.Results/methodology:We demonstrate that the cell number, mean area, thickness and volume were noninvasively measured by using DHM. The cell number was stable over time, but the two cell lines showed changes of cell area and cell irregularity after treatment. The cell volume in etoposide-treated cells was decreased, whereas untreated cells showed stable volume.Conclusion:Our results provide proof of concept for using DHM combined with antibody-based microarray technology for detecting morphological changes in captured cells.

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“…Roles include nutrient supply to the fetus, removal from the fetus of metabolic waste and hormone production. Placental phenotypes for intrauterine growth restriction (McCarthy et al 2007, Struwe et al 2010, pre-eclampsia (Hass et al 2006, Dexlin-Mellby et al 2010 and diabetes in pregnancy (Radaelli et al 2003, Zhao et al 2011 have been described, but these have not specifically been studied in the context of maternal obesity. However, animal models have been crucial in delineating the impact of obesity on placental function.…”

Section: Introductionmentioning

confidence: 99%

The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry

Oliva¹,

Barker²,

Riley³

et al. 2012

Journal of Molecular Endocrinology

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Our aim was to study the protein expression profiles of placenta obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section. We used two-dimensional difference gel electrophoresis (2D-DIGE), utilising narrow-range immobilised pH gradient strips that encompassed the broad pH range of 4–5 and 5–6, followed by MALDI-TOF mass spectrometry of selected protein spots. Western blot and quantitative RT-PCR (qRT-PCR) analyses were performed to validate representative findings from the 2D-DIGE analysis. Eight proteins were altered (six down-regulated and two up-regulated on obese placentas). Annexin A5 (ANXA5), ATP synthase subunit beta, mitochondria (ATPB), brain acid soluble protein 1 (BASP1), ferritin light chain (FTL), heterogeneous nuclear ribonucleoprotein C (HNRPC) and vimentin (VIME) were all lower in obese patients. Alpha-1-antitrypsin (A1AT) and stress-70 protein, mitochondrial (GRP75) were higher in obese patients. Western blot analysis of ANXA5, ATPB, FTL, VIME, A1AT and GRP75 confirmed the findings from the 2D-DIGE analysis. For brain acid soluble protein 1 and HNRPC, qRT-PCR analysis also confirmed the findings from the 2D-DIGE analysis. Immunohistochemical analysis was also used to determine the localisation of the proteins in human placenta. In conclusion, proteomic analysis of placenta reveals differential expression of several proteins in patients with pre-existing obesity. These proteins are implicated in a variety of cellular functions such as regulation of growth, cytoskeletal structure, oxidative stress, inflammation, coagulation and apoptosis. These disturbances may have significant implications for fetal growth and development.

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Tissue proteome profiling of preeclamptic placenta using recombinant antibody microarrays

Abstract: we have taken one step further toward de-convoluting the complex features of PE at the molecular level using affinity proteomics.

Cited by 22 publications

References 86 publications

Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer

Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer

Interfacing Antibody-Based Microarrays and Digital Holography Enables Label-Free Detection for Loss of Cell Volume

The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry

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