Westmead Dermatology Cutaneous squamous cell carcinoma or cSCC is a very common malignancy worldwide, and the first as the cause of death from keratinocytic carcinomas. Around 5% of primary cSCCs metastasize to regional or distant body parts, leading to a 5-year survival rate of only 25-35%. Currently, clinical and histopathological assessment is used for the diagnosis of metastatic cSCC, and this is when the disease is already metastasised. Therapies for patients with metastatic cSCCs are lacking due to poor knowledge of the molecular alterations that drive this metastasis.
We had earlier shown that proteomics (large-scale studies of proteins) has the ability to differentiate between subtypes of skin cancer lesions including melanoma and non-melanoma skin cancers. Using a similar approach, we wanted to investigate the proteome of formalin-fixed and paraffin-embedded samples of primary and metastatic cSCC. We were interested in finding molecular markers, and alterations in potential molecular pathways that may be exploited to, firstly, identify primary lesions with the risk of progression to metastatic phenotype, secondly, explain the molecular mechanism/s behind this progression.
Using primary (n=20) and metastatic cSCC (n=25) samples combined with our SWATH-MS workflow, we have identified more than 5000 proteins across all the samples studied of which at least 30 proteins are found to have the potential to discriminate between the two lesion categories. The proteomics data also separated the two lesion groups on principal components analysis. Our preliminary analysis also indicated that small GTPase mediated signalling and regulation of cytoskeleton organisation are associated with cSCC metastasis.
Overall, results from this study will facilitate early and new diagnostic and therapeutic strategies in primary and metastatic cSCC lesions.
Watch this space for further updates on this study.
