The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis

Abstract

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are < 15%. Hence, melanoma detection in earlier stages (stages I–III) maximises the chances of patient survival. We measured the expression of a panel of 17 microRNAs (miRNAs) (MELmiR-17) in melanoma tissues (stage III; n = 76 and IV; n = 10) and serum samples (collected from controls with no melanoma, n = 130; and patients with melanoma (stages I/II, n = 86; III, n = 50; and IV, n = 119)) obtained from biobanks in Australia and Germany. In melanoma tissues, members of the ‘MELmiR-17’ panel were found to be predictors of stage, recurrence, and survival. Additionally, in a minimally-invasive blood test, a seven-miRNA panel (MELmiR-7) detected the presence of melanoma (relative to controls) with high sensitivity (93%) and specificity (≥ 82%) when ≥ 4 miRNAs were expressed. Moreover, the ‘MELmiR-7’ panel characterised overall survival of melanoma patients better than both serum LDH and S100B (delta log likelihood = 11, p < 0.001). This panel was found to be superior to currently used serological markers for melanoma progression, recurrence, and survival; and would be ideally suited to monitor tumour progression in patients diagnosed with early metastatic disease (stages IIIa–c/IV M1a–b) to detect relapse following surgical or adjuvant treatment.

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma

“…Compared with Stark et al, 11 we were able to identify the signature of three different miRNAs with comparable diagnostic sensitivity and specificity to the MELmiR-7. Moreover, although limited by the small sample size, our findings are to be considered reliable since we utilized two different normalization methods compared with the one chosen by Stark et al…”

“…Moreover, miRNAs might also derive from blood and/or endothelial cells. 11 MiRNAs display several properties that make them potentially valuable biomarkers including stability in body fluids, resistance to endogenous RNase activity, prolonged life at room temperature, and resistance to multiple freeze-thaw cycles. 12 A growing body of evidence shows a different pattern of expression of circulating miRNAs between cancer patients and Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma healthy donors 11,[13][14][15][16][17][18][19] ; however, only a limited number of studies have been focused on melanoma.…”

Evaluating cellular microRNA expression in human papillomavirus associated head and neck squamous cell carcinoma

“…For example, Australian studies in Stage IV melanoma patients have identified a panel of miRNAs which associate with progression of disease and prognosis [78,79]. This panel is readily identifiable in plasma, and could potentially be applied clinically [78]. Similarly, studies in lung cancer are far more advanced, and sets of prognostic miRNAs which are identifiable in plasma have been identified and correlated across multiple studies [116][117][118].…”

“…Several other studies, as Research into the use of miRNAs as prognostic biomarkers is far more advanced in other solid human cancers, such as melanoma, breast cancer and lung cancer. For example, Australian studies in Stage IV melanoma patients have identified a panel of miRNAs which associate with progression of disease and prognosis [78,79]. This panel is readily identifiable in plasma, and could potentially be applied clinically [78].…”

“…This data was then used for further analysis. This method has been described and utilised previously in studies pertaining to the use of the Fluidigm system for analysis of microRNA expression [78,79].…”