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Sökning: onr:"swepub:oai:DiVA.org:kth-124469" > Systematic antibody...

  • O'Leary, Patrick C. (författare)

Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer

  • Artikel/kapitelEngelska2013

Förlag, utgivningsår, omfång ...

  • 2013-04-02
  • Springer Science and Business Media LLC,2013
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-124469
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-124469URI
  • https://doi.org/10.1186/1471-2407-13-175DOI
  • https://lup.lub.lu.se/record/3931237URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-203362URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20130708
  • Background: Although omic-based discovery approaches can provide powerful tools for biomarker identification, several reservations have been raised regarding the clinical applicability of gene expression studies, such as their prohibitive cost. However, the limited availability of antibodies is a key barrier to the development of a lower cost alternative, namely a discrete collection of immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a systematic approach to generate and screen affinity-purified, mono-specific antibodies targeting progression-related biomarkers, with a view towards developing a clinically applicable IHC-based prognostic biomarker panel for breast cancer. Methods: We examined both in-house and publicly available breast cancer DNA microarray datasets relating to invasion and metastasis, thus identifying a cohort of candidate progression-associated biomarkers. Of these, 18 antibodies were released for extended analysis. Validated antibodies were screened against a tissue microarray (TMA) constructed from a cohort of consecutive breast cancer cases (n = 512) to test the immunohistochemical surrogate signature. Results: Antibody screening revealed 3 candidate prognostic markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with poor prognosis, whilst increased expression of PDZK1 was associated with good prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1 expression was associated with decreased recurrence-free survival (p < 0.001) and breast cancer-specific survival (BCSS) (p < 0.001). This novel signature was associated with high tumour grade (p < 0.001), positive nodal status (p = 0.029), ER-negativity (p = 0.006), Her2-positivity (p = 0.036) and high Ki67 status (p < 0.001). However, multivariate Cox regression demonstrated that the signature was not a significant predictor of BCSS (HR = 6.38; 95% CI = 0.79-51.26, p = 0.082). Conclusions: We have developed a comprehensive biomarker pathway that extends from discovery through to validation on a TMA platform. This proof-of-concept study has resulted in the identification of a novel 3-protein prognostic panel. Additional biochemical markers, interrogated using this high-throughput platform, may further augment the prognostic accuracy of this panel to a point that may allow implementation into routine clinical practice.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Penny, Sarah A. (författare)
  • Dolan, Roisin T. (författare)
  • Kelly, Catherine M. (författare)
  • Madden, Stephen F. (författare)
  • Rexhepaj, Elton (författare)
  • Brennan, Donal J. (författare)
  • McCann, Amanda H. (författare)
  • Pontén, FredrikUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)fredpont (författare)
  • Uhlén, MathiasKTH,Proteomik(Swepub:kth)u1dulvmw (författare)
  • Zagozdzon, Radoslaw (författare)
  • Duffy, Michael J. (författare)
  • Kell, Malcolm R. (författare)
  • Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-kji (författare)
  • Gallagher, William M. (författare)
  • Uppsala universitetMolekylär och morfologisk patologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:BMC Cancer: Springer Science and Business Media LLC131471-2407

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