Proteomic Profiling of Archived Tissue of Primary Melanoma Identifies Proteins Associated with Metastasis

Abstract

Formalin-fixed paraffin embedded (FFPE) clinical tissues represent an abundant and unique resource for translational proteomic studies. In the US, melanoma is the 5th and 6th most common cancer in men and women, respectively, affecting over 230,000 people annually and metastasising in 5–15% of cases. Median survival time for distant metastatic melanoma is 6–9 months with a 5-year-survival of < 15%. In this study, 24 primary FFPE tumours which have metastasised (P-M) and 24 primary FFPE tumours which did not metastasise (P-NM) were subjected to proteomic profiling. In total, 2750 proteins were identified, of which 16 were significantly differentially expressed. Analysis of TCGA data demonstrated that expression of the genes encoding for 6 of these 16 proteins had a significant effect on survival in cutaneous melanoma. Pathway analysis of the proteomics data revealed mechanisms likely involved in the process of melanoma metastasis, including cytoskeleton rearrangement, extracellular changes and immune system alterations. A machine learning prediction model scoring an AUC of 0.922, based on these 16 differentially expressed proteins was able to accurately classify samples into P-M and P-NM. This study has identified potential biomarkers and key processes relating to melanoma metastasis using archived clinical samples, providing a basis for future studies in larger cohorts.

Genomic and proteomic findings in early melanoma and opportunities for early diagnosis

“…Studies such as these give the groundwork for further developing our understanding of melanoma progression, the pathways and biological processes potentially affected at each stage as well as subtype, and biomarkers for clinical use. 49 ; while only four studies include benign naevi, 50,51 dysplastic naevi 52 and melanoma in situ. 53 Moreover, the use of formalin-fixed paraffin-embedded (FFPE) samples as a reliable source of material for proteomic investigations had only been recently demonstrated.…”

“…A comprehensive review by Sengupta and colleagues (2016) 48 reported on 25 proteomic studies contributing to melanoma research from 2011 to 2016. Most studies have focussed on metastatic melanoma (Table 2), for example, Shapanis (2020) 49 ; while only four studies include benign naevi, 50,51 dysplastic naevi 52 and melanoma in situ 53 . Moreover, the use of formalin‐fixed paraffin‐embedded (FFPE) samples as a reliable source of material for proteomic investigations had only been recently demonstrated 54–58 .…”