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A direct plasma assay of circulating microRNA-210 of hypoxia can identify early systemic metastasis recurrence in melanoma patients.

Ono S, Oyama T, Lam S, Chong K, Foshag LJ, Hoon DS - Oncotarget (2015)

Bottom Line: In serial bloods within individual patients, cf-miR-210 < 3 months prior to disease recurrence significantly increased compared to baseline levels (p = 0.012).Moreover, cf-miR-210 increase significantly correlated with poorer prognosis (p < 0.001).We concluded enhanced cf-miR-210 provides identification of early systemic melanoma recurrence.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.

ABSTRACT
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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Comparison of miR-210 expression in melanoma FFPE samples(A) MiR-210 expression level was significantly higher in LNM or DOM melanoma samples compared to that in PRM (  p = 0.002, < 0.001, respectively). (B) In paired samples in the same patients, DOM had significantly higher miR-210 level than PRM (  p < 0.001).
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Figure 1: Comparison of miR-210 expression in melanoma FFPE samples(A) MiR-210 expression level was significantly higher in LNM or DOM melanoma samples compared to that in PRM (  p = 0.002, < 0.001, respectively). (B) In paired samples in the same patients, DOM had significantly higher miR-210 level than PRM (  p < 0.001).

Mentions: RT-qPCR analysis of total RNA extracted from formalin-fixed paraffin-embedded (FFPE) melanomas confirmed miR-210 expression level was significantly higher in both lymph node metastasis (LNM) and distant organ metastasis (DOM) compared to primary tumors (PRM; Figure 1A; p = 0.002, < 0.001, respectively). Eight PRMs had paired metastases from DOM whereby we could demonstrate miR-210 level was significantly higher in DOM compared to respective PRM in all eight pairs (Figure 1B; p < 0.001). This demonstrated the development of the hypoxic miR-210 relevance to melanoma metastasis occurrence.


A direct plasma assay of circulating microRNA-210 of hypoxia can identify early systemic metastasis recurrence in melanoma patients.

Ono S, Oyama T, Lam S, Chong K, Foshag LJ, Hoon DS - Oncotarget (2015)

Comparison of miR-210 expression in melanoma FFPE samples(A) MiR-210 expression level was significantly higher in LNM or DOM melanoma samples compared to that in PRM (  p = 0.002, < 0.001, respectively). (B) In paired samples in the same patients, DOM had significantly higher miR-210 level than PRM (  p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466669&req=5

Figure 1: Comparison of miR-210 expression in melanoma FFPE samples(A) MiR-210 expression level was significantly higher in LNM or DOM melanoma samples compared to that in PRM (  p = 0.002, < 0.001, respectively). (B) In paired samples in the same patients, DOM had significantly higher miR-210 level than PRM (  p < 0.001).
Mentions: RT-qPCR analysis of total RNA extracted from formalin-fixed paraffin-embedded (FFPE) melanomas confirmed miR-210 expression level was significantly higher in both lymph node metastasis (LNM) and distant organ metastasis (DOM) compared to primary tumors (PRM; Figure 1A; p = 0.002, < 0.001, respectively). Eight PRMs had paired metastases from DOM whereby we could demonstrate miR-210 level was significantly higher in DOM compared to respective PRM in all eight pairs (Figure 1B; p < 0.001). This demonstrated the development of the hypoxic miR-210 relevance to melanoma metastasis occurrence.

Bottom Line: In serial bloods within individual patients, cf-miR-210 < 3 months prior to disease recurrence significantly increased compared to baseline levels (p = 0.012).Moreover, cf-miR-210 increase significantly correlated with poorer prognosis (p < 0.001).We concluded enhanced cf-miR-210 provides identification of early systemic melanoma recurrence.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus