Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Affinity proteomics exploration of melanoma identifies proteins in serum with associations to T-stage and recurrence
KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.ORCID-id: 0000-0002-7674-2014
Visa övriga samt affilieringar
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Cancer och onkologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:kth:diva-202614OAI: oai:DiVA.org:kth-202614DiVA, id: diva2:1078036
Anmärkning

QC 20170302

Tillgänglig från: 2017-03-02 Skapad: 2017-03-02 Senast uppdaterad: 2017-03-13Bibliografiskt granskad
Ingår i avhandling
1. Affinity assays for profiling disease-associated proteins in human plasma
Öppna denna publikation i ny flik eller fönster >>Affinity assays for profiling disease-associated proteins in human plasma
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Affinity-based proteomics offers opportunities for the discovery and validation of disease-associated proteins in human body fluids. This thesis describes the use of antibody-based immunoassays for multiplexed analysis of proteins in human plasma, serum and cerebrospinal fluid (CSF). This high-throughput method was applied with the objective to identify proteins associated to clinical variables. The main work in this thesis was conducted within the diseases of multiple sclerosis and malignant melanoma, as well as mammographic density, a risk factor for breast cancer.

The suspension bead array (SBA) technology has been the main method for the work presented in this thesis (Paper I-IV). SBA assays and other affinity proteomic technologies were introduced for protein profiling of sample material obtained from clinical collaborators and biobanks. Perspectives on the validation of antibody selectivity by means of e.g. immuno-capture mass spectrometry are also provided.

Paper I describes the development and application of a protocol for multiplexed pro- tein profiling of CSF. The analysis of 340 CSF samples from patients with multiple sclerosis and other neurological disease revealed proteins with potential association to disease progression (GAP43) and inflammation (SERPINA3). Paper II continued on this work with an extended investigation of more than 1,000 clinical samples and included both plasma and CSF collected from the same patients. Comparison of disease subtypes and controls revealed five plasma proteins of potential diagnostic relevance, such as IRF8 and GAP43. The previously reported associations for GAP43 and SERPINA3 in CSF was confirmed. Subsequent immunohistochemical analysis of post-mortem brain tissue revealed differential protein expression in disease affected areas. In Paper III, 150 serum samples from patients with cutaneous malignant melanoma were analyzed. Protein profiles from antibody bead arrays suggested three proteins (RGN, MTHFD1L, STX7) of differential abundance between patients with no disease recurrence and low tumor thickness (T-stage 1 and 2) compared to patients with high tumor thickness (T-stage 3 and 4) and disease recurrence. We observed MTHFD1L expression in tissue of a majority of patients, while expression of STX7 in melanoma tissue had been reported previously. Paper IV describes the analysis of protein in plasma in relation to mammographic breast density (MD), one of the strongest risk factors for the development of breast cancers. More than 1,300 women without prior history of breast cancer were screened. Linear associations to MD in two independent sample sets were found for 11 proteins, which are expressed in the breast and involved in tissue homeostasis, DNA repair, cancer development and/or progression in MD.

In conclusion, this thesis describes the use of multiplexed antibody bead arrays for protein profiling of serum, plasma and CSF, and it shortlists disease associated proteins for further validation studies. 

Ort, förlag, år, upplaga, sidor
Stockholm: KTH Royal Institute of Technology, 2017. s. 89
Serie
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:6
Nyckelord
proteomics, affinity proteomics, immunoassay, antibody microarray, suspension bead array, protein profiling, immuno-capture, plasma, serum, cerebrospinal fluid, biomarker discovery, multiple sclerosis, malignant melanoma, mammographic breast density
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Forskningsämne
Bioteknologi
Identifikatorer
urn:nbn:se:kth:diva-202616 (URN)978-91-7729-297-5 (ISBN)
Disputation
2017-03-31, Inghesalen, KI, Tomtebodavägen 18A, Solna, 10:00 (Engelska)
Opponent
Handledare
Anmärkning

QC 20170302

Tillgänglig från: 2017-03-02 Skapad: 2017-03-02 Senast uppdaterad: 2017-03-06Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Personposter BETA

Byström, SannaUhlén, MatthiasSchwenk, Jochen M.

Sök vidare i DiVA

Av författaren/redaktören
Byström, SannaFredolini, ClaudiaDrobin, KimiUhlén, MatthiasSchwenk, Jochen M.
Av organisationen
Proteomik och nanobioteknologi
Cancer och onkologiMedicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Sök vidare utanför DiVA

GoogleGoogle Scholar

urn-nbn

Altmetricpoäng

urn-nbn
Totalt: 113 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf