Project 15 – Analysis of circulating biomarkers for early detection of melanoma recurrence.

Hypothesis: Identification of non-invasive biomarkers to monitor patients after surgical resection of localized primary cutaneous malignant melanoma (CMM) is fundamental for the detection of early clinical recurrence.

Background and Significance: Men and women exhibit different age patterns of melanoma incidence and different prognosis. Women are often diagnosed during their reproductive years and have a better prognosis that is not completely explained by differences in the stage at diagnosis or in the biology of the lesions. Large amount of expression profiles is available in public repositories and could be investigated with a special focus on gender-specific prognostic signatures according to age classes. At the same time, collection of primary lesion tissues and of longitudinal serum/plasma samples together with patient follow-up could allow prospective validation of prognostic signatures and identification of novel circulating markers to monitor patients.

Objectives: To look for gender and age-specific markers of melanoma recurrence by focussing on meta-analysis of expression profiles of CMM primary lesions and ensuing clinical history (recurrent free versus metastatic disease, response to treatment, 5 years survival) integrated with information of circulating sex hormone levels and miRNAs (cf-miRNAs). To establish a data base of longitudinal levels of sex hormones and cf-miRNAs from plasma/serum samples collected from patients surgically treated for localized primary CMM.

The mathematical part of this project will deal with data mining, identification of gene expression signatures associated with survival information (multivariable cox regression modelling, with or without penalization, or other techniques to detect important variables able to predict patient prognosis), sample stratification according to specific covariates.

The student will spend 6 months at the University of Lausanne to measure sex hormones and will also work with the team of Dr Gian Paolo Dotto.

Related readings

Nosrati, A. & Wei, M. L. Sex disparities in melanoma outcomes: the role of biology. Arch Biochem Biophys 563, 42-50 (2014).

Marzagalli, M. et al. Estrogen Receptor beta in Melanoma: From Molecular Insights to Potential Clinical Utility. Front Endocrinol 7, 140 (2016).