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Byström, S., Eklund, M., Hong, M.-G., Fredolini, C., Eriksson, M., Czene, K., . . . Gabrielson, M. (2018). Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density. Breast Cancer Research, 20, Article ID 14.
Open this publication in new window or tab >>Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density
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2018 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 20, article id 14Article in journal (Refereed) Published
Abstract [en]

Background: Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density. Methods: Plasma samples from 1329 women in the Swedish KARMA project, without prior history of breast cancer, were profiled with antibody suspension bead array (SBA) assays. Two sample sets comprising 729 and 600 women were screened by two different SBAs targeting a total number of 357 proteins. Protein targets were selected through searching the literature, for either being related to breast cancer or for being linked to the extracellular matrix. Association between proteins and absolute area-based breast density (AD) was assessed by quantile regression, adjusting for age and body mass index (BMI). Results: Plasma profiling revealed linear association between 20 proteins and AD, concordant in the two sets of samples (p < 0.05). Plasma levels of seven proteins were positively associated and 13 proteins negatively associated with AD. For eleven of these proteins evidence for gene expression in breast tissue existed. Among these, ABCC11, TNFRSF10D, F11R and ERRF were positively associated with AD, and SHC1, CFLAR, ACOX2, ITGB6, RASSF1, FANCD2 and IRX5 were negatively associated with AD. Conclusions: Screening proteins in plasma indicates associations between breast density and processes of tissue homeostasis, DNA repair, cancer development and/or progression in breast cancer. Further validation and follow-up studies of the shortlisted protein candidates in independent cohorts will be needed to infer their role in breast density and its progression in premenopausal and postmenopausal women.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2018
Keywords
Mammographic breast density, Plasma, Protein profiling, Suspension bead array, Affinity proteomics, KARMA cohort
National Category
Clinical Medicine
Identifiers
urn:nbn:se:kth:diva-223790 (URN)10.1186/s13058-018-0940-z (DOI)000425114200001 ()29444691 (PubMedID)2-s2.0-85042063089 (Scopus ID)
Funder
Swedish Research CouncilThe Kamprad Family FoundationKnut and Alice Wallenberg FoundationSwedish Cancer SocietyScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180307

Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-07Bibliographically approved
Chen, Z., Dodig-Crnkovic, T., Schwenk, J. M. & Tao, S.-c. (2018). Current applications of antibody microarrays. Clinical Proteomics, 15, Article ID 7.
Open this publication in new window or tab >>Current applications of antibody microarrays
2018 (English)In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 15, article id 7Article, review/survey (Refereed) Published
Abstract [en]

The concept of antibody microarrays is one of the most versatile approaches within multiplexed immunoassay technologies. These types of arrays have increasingly become an attractive tool for the exploratory detection and study of protein abundance, function, pathways, and potential drug targets. Due to the properties of the antibody microarrays and their potential use in basic research and clinical analytics, various types of antibody microarrays have already been developed. In spite of the growing number of studies utilizing this technique, few reviews about antibody microarray technology have been presented to reflect the quality and future uses of the generated data. In this review, we provide a summary of the recent applications of antibody microarray techniques in basic biology and clinical studies, providing insights into the current trends and future of protein analysis.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Antibody microarray, Signalling, Drug mechanism, Clinical application, Systems biology, Technology advances
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-224692 (URN)10.1186/s12014-018-9184-2 (DOI)000426761800001 ()29507545 (PubMedID)2-s2.0-85042706257 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation
Note

QC 20180322

Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Persson, M., Zandian, A., Wingard, L., Nilsson, H., Sjostedt, E., Johansson, D., . . . Nilsson, P. (2018). Searching for Novel Autoantibodies with Clinical Relevance in Psychiatric Disorders. Paper presented at 6th Biennial Conference of the Schizophrenia-International-Research-Society (SIRS), APR 04-08, 2018, Florence, Italy. Schizophrenia Bulletin, 44, S120-S121
Open this publication in new window or tab >>Searching for Novel Autoantibodies with Clinical Relevance in Psychiatric Disorders
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2018 (English)In: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 44, p. S120-S121Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-226780 (URN)000429541800296 ()
Conference
6th Biennial Conference of the Schizophrenia-International-Research-Society (SIRS), APR 04-08, 2018, Florence, Italy
Funder
EU, European Research Council, 670821
Note

QC 20180522

Available from: 2018-05-22 Created: 2018-05-22 Last updated: 2018-05-22Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umea Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population. Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data. Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort. Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-222452 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)2-s2.0-85021081885 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180209

Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2018-02-09Bibliographically approved
Uhlén, M., Zhang, C., Lee, S., Sjöstedt, E., Fagerberg, L., Bidkhori, G., . . . Ponten, F. (2017). A pathology atlas of the human cancer transcriptome. Science, 357(6352), 660-+
Open this publication in new window or tab >>A pathology atlas of the human cancer transcriptome
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2017 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 357, no 6352, p. 660-+Article in journal (Refereed) Published
Abstract [en]

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.

Place, publisher, year, edition, pages
American Association for the Advancement of Science, 2017
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-214334 (URN)10.1126/science.aan2507 (DOI)000407793600028 ()2-s2.0-85028362951 (Scopus ID)
Funder
Swedish Cancer SocietyScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg FoundationSwedish Research Council
Note

QC 20170913

Available from: 2017-09-13 Created: 2017-09-13 Last updated: 2018-02-28Bibliographically approved
Omazic, B., Ayoglu, B., Löhr, M., Segersvärd, R., Verbeke, C., Magalhaes, I., . . . Ringden, O. (2017). A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer. Journal of immunotherapy (1997), 40(4), 132-139
Open this publication in new window or tab >>A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer
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2017 (English)In: Journal of immunotherapy (1997), ISSN 1524-9557, E-ISSN 1537-4513, Vol. 40, no 4, p. 132-139Article in journal (Refereed) Published
Abstract [en]

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A∗01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Place, publisher, year, edition, pages
Lippincott Williams and Wilkins, 2017
Keywords
HSCT, pancreatic adenocarcinoma, radical surgery
National Category
Cancer and Oncology Immunology
Identifiers
urn:nbn:se:kth:diva-207424 (URN)10.1097/CJI.0000000000000164 (DOI)000398850800003 ()2-s2.0-85016172220 (Scopus ID)
Note

QC 20170524

Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2017-06-02Bibliographically approved
Thul, P. J., Åkesson, L., Wiking, M., Mahdessian, D., Geladaki, A., Ait Blal, H., . . . Lundberg, E. (2017). A subcellular map of the human proteome. Science, 356(6340), Article ID 820.
Open this publication in new window or tab >>A subcellular map of the human proteome
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2017 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 356, no 6340, article id 820Article in journal (Refereed) Published
Abstract [en]

Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.

Place, publisher, year, edition, pages
American Association for the Advancement of Science, 2017
Keywords
antibody, proteome, biology, cells and cell components, disease incidence, image analysis, physiological response, protein, proteomics, spatial distribution, Article, cell organelle, cellular distribution, human, human cell, immunofluorescence microscopy, mass spectrometry, priority journal, protein analysis, protein localization, protein protein interaction, single cell analysis, transcriptomics
National Category
Cell Biology
Identifiers
urn:nbn:se:kth:diva-216588 (URN)10.1126/science.aal3321 (DOI)000401957900032 ()2-s2.0-85019201137 (Scopus ID)
Note

QC 20171208

Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2017-12-08Bibliographically approved
Lourido, L., Ayoglu, B., Fernandez-Tajes, J., Oreiro, N., Henjes, F., Hellstroem, C., . . . Blanco, F. J. (2017). Discovery of circulating proteins associated to knee radiographic osteoarthritis. Scientific Reports, 7, Article ID 137.
Open this publication in new window or tab >>Discovery of circulating proteins associated to knee radiographic osteoarthritis
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 137Article in journal (Refereed) Published
Abstract [en]

Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:kth:diva-205464 (URN)10.1038/s41598-017-00195-8 (DOI)000396868900019 ()28273936 (PubMedID)2-s2.0-85036578428 (Scopus ID)
Available from: 2017-05-22 Created: 2017-05-22 Last updated: 2017-05-22Bibliographically approved
Pin, E., Henjes, F., Hong, M.-G., Wiklund, F., Magnusson, P., Bjartell, A., . . . Schwenk, J. M. (2017). Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer. Journal of Proteome Research, 16(1), 204-216
Open this publication in new window or tab >>Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer
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2017 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, no 1, p. 204-216Article in journal (Refereed) Published
Abstract [en]

There is a demand for novel targets and approaches to diagnose and treat prostate cancer (PCA). In this context, serum and plasma samples from a total of 609 individuals from two independent patient cohorts were screened for IgG reactivity against a sum of 3833 human protein fragments. Starting from planar protein arrays with 3786 protein fragments to screen 80 patients with and without PCA diagnosis, 161 fragments (4%) were chosen for further analysis based on their reactivity profiles. Adding 71 antigens from literature, the selection of antigens was corroborated for their reactivity in a set of 550 samples using suspension bead arrays. The antigens prostein (SLC45A3), TATA-box binding protein (TBP), and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) showed higher reactivity in PCA patients with late disease compared with early disease. Because of its prostate tissue specificity, we focused on prostein and continued with mapping epitopes of the 66-mer protein fragment using patient samples. Using bead-based assays and 15-mer peptides, a minimal peptide epitope was identified and refined by alanine scanning to the KPxAPFP. Further sequence alignment of this motif revealed homology to transmembrane protein 79 (TMEM79) and TGF-beta-induced factor 2 (TGIF2), thus providing a reasoning for cross-reactivity found in females. A comprehensive workflow to discover and validate IgG reactivity against prostein and homologous targets in human serum and plasma was applied. This study provides useful information when searching for novel biomarkers or drug targets that are guided by the reactivity of the immune system against autoantigens.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
Keywords
autoimmunity, prostate cancer, prostein, planar microarray, suspension bead array, profiling epitope mapping, Human Protein Atlas, antigen, peptide
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-201244 (URN)10.1021/acs.jproteome.6b00620 (DOI)000391782100019 ()2-s2.0-85017653060 (Scopus ID)
Note

QC 20170216

Available from: 2017-02-16 Created: 2017-02-16 Last updated: 2017-11-29Bibliographically approved
Idborg, H., Zandian, A., Hellstrom, C., Mattsson, C., Fredolini, C., Uhlén, M., . . . Nilsson, P. (2017). PROTEIN PROFILING IN PLASMA REVEALS MOLECULAR SUBGROUPS IN SYSTEMIC LUPUS ERYTHEMATOSUS. Paper presented at 37th European Workshop on Rheumatology Research (EWRR), MAR 02-04, 2017, Athens, GREECE. Annals of the Rheumatic Diseases, 76, A52-A52
Open this publication in new window or tab >>PROTEIN PROFILING IN PLASMA REVEALS MOLECULAR SUBGROUPS IN SYSTEMIC LUPUS ERYTHEMATOSUS
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. A52-A52Article in journal (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:kth:diva-216642 (URN)10.1136/annrheumdis-2016-211052.1 (DOI)000411783100070 ()
Conference
37th European Workshop on Rheumatology Research (EWRR), MAR 02-04, 2017, Athens, GREECE
Note

QC 20171031

Available from: 2017-10-31 Created: 2017-10-31 Last updated: 2017-10-31Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8141-8449

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