A direct plasma assay of circulating microRNA-210 of hypoxia can identify early systemic metastasis recurrence in melanoma patients
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Shigeshi Ono1, Takashi Oyama1, Stella Lam1, Kelly Chong1, Leland J. Foshag2, Dave S.B. Hoon1
1Department of Molecular Oncology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA
2Division of Surgical Oncology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA
Dave S.B. Hoon, e-mail: firstname.lastname@example.org
Keywords: cell-free microRNA, diagnosis, plasma, metastatic melanoma recurrence, LDH
Received: January 06, 2015 Accepted: January 10, 2015 Published: February 05, 2015
Circulating cell-free(cf) microRNAs (miRNAs) have been reported to exist in plasma. MicroRNA-210(miR-210) is known to play important roles in the tumor hypoxic state. We hypothesized that the expression levels of cf-miR-210 in plasma would predict early clinical recurrence in melanoma patients. A direct miRNA assay on plasma (RT-qPCR-DP) was developed to improve cf-miRNA assay logistics, eliminate RNA extraction, and reduce specimen amount required. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) melanoma tissues (n = 108) and assessed by RT-qPCR. Plasma (10 μl; n = 264) was procured from AJCC Stage III/IV patients in phase III clinical trials. A RT-qPCR-DP was performed to detect cf-miR-210. MiR-210 was significantly higher in metastatic tumors compared to primary tumors. Cf-miR-210 was significantly higher in melanoma patients versus healthy donor controls. In serial bloods within individual patients, cf-miR-210 < 3 months prior to disease recurrence significantly increased compared to baseline levels (p = 0.012). ROC curve analysis demonstrated that patients with elevated cf-miR-210 were more likely to have disease recurrence. Moreover, cf-miR-210 increase significantly correlated with poorer prognosis (p < 0.001). Lactate dehydrogenase (LDH) level was also assessed within patients, and the AIC values for proportional hazards regression models of cf-miR-210(120.01) and LDH (122.91) demonstrated that cf-miR-210 is a better recurrence indicator. We concluded enhanced cf-miR-210 provides identification of early systemic melanoma recurrence.
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