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

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.