It is essential to detect and control asymptomatic brain metastases, since their progression can cause a significant deterioration in quality of life, neurological functions and neurologic death.
In this project, the biomarker repertoire of prospectively collected baseline blood samples from 35 melanoma patients with intracranial and extracranial metastases and 61 samples from melanoma patients with extracranial-only metastatic disease will be analysed (discovery cohort). The validation cohort consists of 30 extracranial-only metastatic patients, 30 intracranial and extracranial patients and 30 intracranial-only metastatic patients.
To assess the autoantibody repertoire (> 21 000 IgG and IgA) of the two groups HuProt™ Human Proteome Microarrays v4 (CDI Labs) will be used. To validate autoantibodies of interest, focused arrays will be performed. Differentially expressed serum microRNAs will be identified via Ion Torrent sequencing (Thermo Fisher). To validate the identified miRNA targets of interest a TaqMan MicroRNA Assay (Thermo Fisher) will be performed. To obtain a more generally applicable marker for damage to the blood-brain barrier, plasma brain-derived cell-free DNA from astrocytes, oligodendrocytes and neurons will be investigated. A QIAseq Targeted Methyl Panel (Qiagen) will be set up based on targets already identified in literature for brain-specific clusters of CG. Brain-specific cell-free DNA markers of interest will be validated by means of a qPCR.
Since the identification and quantification of specific combinations of circulating biomarkers may enable a more precise assessment for screening and prognostic purposes in metastatic melanoma patients, a multi-omic model will be set up.