The Analysis of Inflammation-Related Proteins in a Cargo of Exosomes Derived from the Serum of Uveal Melanoma Patients Reveals Potential Biomarkers of Disease Progression

Abstract

Background: Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. However, despite relatively good knowledge about the histological and genetic risk factors for metastasis development, there is no specific biomarker that would allow early detection of UM progression. Recently, exosomes and their molecular cargo have been widely studied in the search for potential biomarkers in several cancers. The purpose of this study was to analyze the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors. Methods: The exosomes were isolated from the serum of primary and metastatic UM patients and healthy donors. Using multiplex immunoassay technology, we analyzed the concentration of 37 inflammation-related proteins in obtained exosomes. Results: The analysis of protein cargo showed several molecules related to inflammation, such as interferon-gamma, interleukin 2, 22 and 12(p40), Pentraxin-3, TNFSF13B and TNFSF8 which were significantly enriched in metastatic UM exosomes. We showed a significant correlation between the disease stage and the concentration of these inflammation-related proteins from exosomal cargo. Conclusions: Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease.

Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells

“…Thus, reduced gp130 expression as a primary cause of IL-6 unresponsiveness could be excluded. However, it may change the sensitivity of cells to stimulation with IL-6 or other members of the IL-6 cytokine family; for example, IL-11 was observed in highly elevated concentrations in exosomes derived from primary uveal melanoma patients, with a further upregulation in the case of metastasis, indicating a role in uveal melanoma progression [ 36 ]. Activation of Erk2, controlling expression of gp130 [ 37 ], was recently shown to be inhibited by chelidonine, providing a possible mechanism for the reduced expression of gp130 [ 18 , 23 ].…”

Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma

“…IL-11 is a pleiotropic interleukin involved in tumor development. IL-11 has been shown to be elevated in colorectal cancer and in the exosomes of metastatic uveal melanoma and is associated with poor prognosis in melanoma [ 22 , 23 , 24 , 25 ]. It is known that phenotype switching is characteristic of melanoma, where proliferative cells tend to be non-invasive, while invasive cells tend to be non-proliferative, a process regulated by the Wnt signaling pathway [ 26 , 27 , 28 ].…”

Is Tissue Still the Issue? The Promise of Liquid Biopsy in Uveal Melanoma

“…These interleukins are involved in both pro and anti-tumor response. IFN-γ was also found upregulated in exosomes derived from metastatic disease, which is correlated to metastases and overall more extensive disease [ 92 ]. As IFN-γ was highly upregulated in only the metastatic patients, this is potentially an exosomal marker for monitoring disease progression.…”