Review article| Volume 99, ISSUE 1, P9-16, July 2020

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Proteomics: An emerging approach for the diagnosis and classification of cutaneous squamous cell carcinoma and its precursors

  • Ali Azimi
    Centre for Translational Skin Research, The University of Sydney, Westmead, Australia

    Department of Dermatology, Westmead Hospital, Westmead, Australia
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  • Kimberley L. Kaufman
    Department of Neurosurgery, Chris O’Brien Lifehouse, Camperdown, Australia

    Discipline of Pathology, The University of Sydney, Camperdown, Australia
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  • Jennifer Kim
    Department of Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Australia
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  • Marina Ali
    Centre for Translational Skin Research, The University of Sydney, Westmead, Australia

    Department of Dermatology, Westmead Hospital, Westmead, Australia
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  • Graham J. Mann
    Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, Australia

    Melanoma Institute Australia, The University of Sydney, Wollstonecraft, Australia
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  • Pablo Fernandez-Penas
    Corresponding author at: Dermatology Department, Westmead Hospital, D5a, CD Block, Hawkesbury Road, Westmead, NSW 2145, Australia.
    Centre for Translational Skin Research, The University of Sydney, Westmead, Australia

    Department of Dermatology, Westmead Hospital, Westmead, Australia
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      • Discrepancies between the histologic analyses of cSCC and its precursors make their diagnosis difficult.
      • Protein biomarkers can ameliorate the negative impact of mis- or delayed diagnosis on patient outcome.
      • Proteomics is useful for the identification of new cSCC biomarkers and therapeutic targets.
      • Skin sampling by tape-stripping offers a non-invasive approach to cSCC biomarker discovery.


      Cutaneous squamous cell carcinoma (cSCC) and its precursors, actinic keratosis (AK) and Bowen’s disease (BD), are the most common types of keratinocytic skin lesions (KSL) which account for the majority of non-melanoma skin cancer lethality. Currently, clinical and histopathological criteria are used for the diagnosis, classification and therapeutic intervention of KSLs, however discrepancies exist between the clinical presentations and histologic analyses of these lesions, making the diagnosis difficult. The identification of biomarkers as companion diagnostics for accurately stratifying KSL types is required to support the paradigm shift in current cancer care to personalised, precision medicine and ameliorate the negative impact of misdiagnoses or delayed diagnoses on patient outcome. Also, it is essential to elaborate on the poorly defined molecular modifications required for the initiation, development and progression of KSL from normal keratinocytes. By harnessing recent technological advances in molecular profiling techniques, it is anticipated that greater insight into the various combinations of proteomic events or alternative pathways underlying carcinogenesis will be gained. This review will explore recent genomic studies in KSL followed by assessing the feasibility and significance of mass spectrometry-based proteomics profiling as a promising approach to a better understanding of the oncogenic pathways underpinning the formation and progression of KSL lesions and in aiding the identification of novel biomarkers and new therapeutic targets. The development of non-invasive tools such as tape-stripping coupled with proteomic analysis alone or in conjunction with imaging and genomic technologies will complement existing clinical and histopathological parameters, leading to an improvement in patient outcomes.


      AK (actinic keratosis), BD (Bowen’s disease), cSCC (cutaneous squamous cell carcinoma), KSL (keratinocytic skin lesions), SWATH-MS (sequential window acquisition of all theoretical mass spectra)


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      Dr Ali Azimi is a post-doctoral research fellow with the Department of Dermatology at the University of Sydney, Australia. Dr Azimi, in the past few years, has been involved in utilising cutting-edge mass-spectrometry-based proteomics to resolve the molecular landscape of skin cancers including melanoma and non-melanoma skin cancers. As alternative to biopsy, he has also investigated the use of non-invasive tape-stripping method for proteomic investigation of skin cancers. In collaboration with experts in histopathology, genomics and proteomics, Dr Azimi aims to work towards the introduction of multi-modality research studies in skin cancers to allow a better understanding of the lesions.