Background: Biopsy and histopathology is the primary tool for diagnosis of melanoma. However, such aggressive methods can lead to scaring, and risk quality of life. Further, increased usage has not reduced mortality rate. There is a demand to find alternative non-invasive methods of diagnosis such as tape-stripping.
Aim & Objectives: To investigate proteomics combined with tape-stripping as a diagnostic tool for melanoma in benign pigmented lesions.
Method: Adhesive tape-strips (1-10 discs) were applied to the stratum corneum of melanocytic lesions with matched normal. Samples consisted of matched normal non-lesional (n=95), benign naevi (n=21), dysplastic naevi (n=38), melanoma in situ (n=24), and invasive melanomas (n=12). Following preparation and proteolytic digestion, the samples’ proteome was analysed in a Thermo Scientific Orbitrap Eclipse Tribrid mass spectrometer using data-independent acquisition (DIA) workflow. Differential abundance and enrichment analysis were then performed on the proteomic data. Followed by machine learning cross validation to assess classification potential of top significant proteins.
Results: We identified 1196 proteins and 6261 peptides total across the 95 samples studied. Cross validation of top 6 significant differentially abundant proteins ( p-value <0.05, FC >1.5 FC<-1.5) between benign naevi and invasive melanoma revealed good model performance. Additionally, semi-supervised principle component analysis were able to visualise clusters between benign and malignant groups while k-means clustering revealed intermediate lesions aligned with either benign or malignant clusters.
Conclusion: This preliminary study demonstrates the successful detection of proteins in tape-stripped samples of benign nevi, dysplastic nevi, melanoma in situ, and melanoma using DIA methodology. Further exploration and validation of this technique provides a promising avenue for non-invasive diagnosis of melanoma in benign pigmented lesion