Plasma Markers for Identifying Patients with Metastatic Melanoma

Abstract

Purpose With the rising incidence of melanoma, more patients are undergoing surveillance for disease recurrence. Our purpose was to study levels of proteins that might be secreted in the blood of patients with metastatic melanoma that can be used for monitoring these individuals. Methods Genome-wide gene expression data were used to identify abundantly expressed genes in melanoma cells that encode for proteins likely to be present in the blood of cancer patients based on high expression levels in tumors. ELISA assays were employed to measure proteins in plasma of 216 individuals; 108 metastatic melanoma patients and 108 age- and gender-matched patients with resected stage I/II disease split into equal-sized training and test cohorts. Results Levels of seven markers, CEACAM, ICAM-1, osteopontin, MIA, GDF-15, TIMP-1 and S100B, were higher in patients with unresected stage IV disease than in patients with resected stage I/II disease. 81% of the stage I/II patients in the training set had no marker elevation, whereas 69% of the stage IV patients had elevation of at least one marker (p<0.0001). Receiver operating characteristic curves for the markers in combination in these two patient populations had an AUC of 0.79 in the training set, 0.8 in the test set. A CART model developed in the training set further improved the AUC in the test set to 0.898. Conclusions Plasma markers, particularly when assessed in combination, can be used to monitor patients for disease recurrence and can compliment currently used LDH and imaging studies; prospective validation is warranted.

Combining multiple serum biomarkers in tumor diagnosis: A clinical assessment

“…Moreover, unless presented with evidence of a high probability of having cancer, patients are also reluctant to undergo biopsy. Therefore, an emphasis has been placed on tumor markers and their role in assisting with screening and diagnosing tumors (2)(3)(4)(5). Certain tumor markers are detected in serum when tumors are at an early stage, rendering the identification of tumor markers an area of interest.…”

Growth/differentiation factor-15 and its role in peripheral nervous system lesion and regeneration

“…Obese patients express high levels of GDF-15, especially patients suffering from type II diabetes (Lajer et al, 2010). GDF-15 is associated with keratinocyte differentiation and several skin diseases, such as skin sclerosis and melanoma Kluger et al, 2011;Yanaba et al, 2012). GDF-15 also regulates osteoclastic differentiation through inhibiting carbonic anhydrase II and cathepsin K (Hinoi et al, 2012;Vanhara et al, 2009).…”

The role of osteopontin expression in melanoma progression

“…OPN is a prognostic marker in a variety of cancers [30,[39][40][41]. In metastatic and primary melanomas, OPN has also been suggested to be a novel promising biomarker for the detection of metastases in patients with primary melanomas [24,[42][43][44][45]. Atai et al…”