Poster Presentation ASDR Annual Scientific Meeting 2019

SWATH proteomic analysis can discriminate between actinic keratosis, Bowen’s disease and cutaneous squamous cell carcinoma  (#40)

Ali Azimi 1 2 , Pengyi Yang 3 , Marina Ali 1 2 , Vicki Howard 4 , Graham J Mann 5 6 , Kimberley L Kaufman 7 8 , Pablo Fernandez-Penas 1 2
  1. The Department of Dermatology, Westmead Hospital, The University of Sydney, Westmead, NSW 2145, Australia
  2. Centre for Translational Skin Research, The University of Sydney, Westmead, NSW, Australia
  3. School Mathematics and Statistics, The University of Sydney, Camperdown, NSW, Australia
  4. Dermatopathology, Skin and Cancer Foundation Australia, Darlinghurst, NSW, Australia
  5. Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, Australia
  6. Melanoma Inistitute Australia, The University of Sydney, Wollstonecraft, NSW, Australia
  7. School of Molecular Bioscience, Faculty of Science, The University of Sydney, Camperdown , NSW 2050, Australia
  8. Brain and Mind Centre, The University of Sydney, Camperdown, NSW 2050, Australia

Actinic keratosis (AK), Bowen’s disease (BD) and cutaneous squamous cell carcinoma (cSCC) are heterogeneous keratinocytic skin lesions (KSL). Biomarkers that can accurately stratify these lesion types are needed to support a new paradigm of personalised, precise management of skin neoplasia. In this paper, we used the SWATH proteomics workflow to analyse formalin-fixed paraffin embedded (FFPE) samples of normal skin and KSL including well differentiated (WD), moderately differentiated (MD) and poorly differentiated (PD) cSCC. We identified and quantified 3574 proteins across 93 samples studied. Differential abundance analysis identified 19, five and six protein markers exclusive to AK, BD and cSCC lesions, respectively. Among cSCC lesions of various levels of tumour differentiation, 118, 230 and 17 proteins showed potential as biomarkers of WD-, MD- and PD-cSCC lesions, respectively. Bioinformatics analysis revealed that AK and cSCC lesions were associated with decreased apoptosis and BD lesions with over-representation of DNA damage repair pathway.  Differential expression of FGFR2 alternative splicing, Rho GTPase signalling, and RNA metabolism proteins were associated with the level of cSCC tumour differentiation. Proteome profiles also separated all KSL subtypes on principal components analysis. Overall, protein markers have excellent potential to discriminate KSL subtypes and facilitate new diagnostic and therapeutic strategies. 

 

  • Are you an ECR (within 4 years of conferring of PhD)?: No
  • Are you an ECR (within 4 years of conferring of PhD)?: No