Westmead Dermatology By: Steven Jabbour
Having recently graduated, I decided to join the dermatology team at Westmead to pursue research in a field I am passionate about. Among the many exciting projects currently being undertaken by the team, the idea of a ‘scar-less’ biopsy was an interesting one that stood out to me.
Actinic keratosis and Bowen’s disease are common premalignant skin lesions that have the potential to progress into malignant cutaneous squamous cell carcinomas (cSCC); collectively, these are referred to as keratinocytic skin lesions (KSL) and are often caused by sun exposure. The prognosis of the premalignant lesions differs from that of the malignant cSCCs, hence, it is important to be able to discern between them during a diagnosis. A biopsy followed by histopathological assessment is currently the most common diagnostic technique for KSLs, however, it has some significant limitations despite being considered the gold standard. Its invasive nature results in permanent scarring, discomfort, and troublesome aftercare; histopathology reports rely on pathologist interpretation and can be unclear, leading to misdiagnosis; and thirdly, surgery is costly.
We used SWATH mass spectrometry proteomics to analyse proteins collected non-invasively from KSLs using tape-stripping. Tape-stripping is a technique that collects cells from the surface of the stratum corneum by applying a small adhesive disk, almost like a sticker, to the surface of the skin.
From 61 total tape-stripped samples consisting of actinic keratosis, Bowen’s disease, cSCC, and normal epidermis, our SWATH mass spectrometry analysis was able to identify 4794 unique proteins. Potentially important biomarkers that could discriminate the KSL subtypes from each other as well as from the normal epidermis were identified. Bioinformatics analysis revealed that the functional significance of these proteins was correlated with KSL pathophysiology and that the potential activation of carcinogenic pathways coupled with the inactivation of tumour-suppressive pathways may contribute to the progression of premalignant KSLs into malignant ones.
This study demonstrated the successful application of tape-stripping coupled with SWATH proteomics for extracting and quantifying proteins from KSLs. The utilisation of this technique may become a widely preferred alternative diagnostic technique for KSLs as it not only overcomes the limitations associated with an invasive biopsy but allows for routine monitoring of the patient’s lesion.
