Proteomic profiling of extracellular vesicles suggests Collectin10 as potential biomarker in relapsing head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Developing new therapies has been ongoing for many decades, however, the 5-year overall survival rate remains comparably low and has not improved significantly. Treatment failure in HNSCC patients is common, especially in recurrences, and results in a poorer prognosis. Therefore, a better understanding of the disease is crucial to detect HNSCC recurrences at an early stage. HNSCC-ssociated extracellular vesicles (EVs), have been shown to suppress the immune system and thereby promote tumor progression. However, it is still unclear which pathways play a pivotal role in relapse or in remission. Contamination-free plasma EVs were purified using the EXÖBead® technology and EVs proteins underwent holistic proteome profiling by high-resolution mass spectrometry. COLEC10 appears to be the most regulated EVs protein and therefore has been chosen for further analysis and validation. Furthermore PanEV+ COLEC10+ and PanEV+ CD45Neg COLEC10+ of plasma EVs-EXÖBead complexes also showed a higher expression in relapsed patients compared to remission. Gene ontology analyses suggested that the relapse-upregulated proteins are significantly enriched in pathways for collagen trimer and chain formation, the complement system activation and in the tumor necrosis factor like domain superfamily related pathway. The remission-pregulated proteins were significantly enriched in early endosome or lysosomal membrane formation, membrane stability, mRNA stability and in ubiquitin protein ligase binding. According to common tissue RNA-seq database elevated COLEC10 gene has been associated with shorter survival in female patient and observed from different clinical cohort. Our results indicate that increased protein expression in EVs of patients with recurrent disease might contribute to disease progression with COLEC10 as potential biomarker in HNSCC.