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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 change in baseline LDH vs change in cf-miR-210 dCq(A) ROC analysis was performed to determine the cutoff for LDH changes (LDH Cutoff: 1.175-fold change from baseline; AUC = 0.535). Change in LDH level did not predict recurrence (  p = 0.810, AIU = 122.91) (A), while change in cf-miR-210 was a significant predictor of recurrence (B) (  p = 0.15, AIU = 120.01). Positive: Recurrence < 2 yrs, Negative: No recurrence > 5 yrs.
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Figure 6: Comparison of change in baseline LDH vs change in cf-miR-210 dCq(A) ROC analysis was performed to determine the cutoff for LDH changes (LDH Cutoff: 1.175-fold change from baseline; AUC = 0.535). Change in LDH level did not predict recurrence (  p = 0.810, AIU = 122.91) (A), while change in cf-miR-210 was a significant predictor of recurrence (B) (  p = 0.15, AIU = 120.01). Positive: Recurrence < 2 yrs, Negative: No recurrence > 5 yrs.

Mentions: LDH levels of the recurrent patients in blood were also analyzed. It was from either the same day or < 30 days of the plasma for which cf-miR-210 was assessed. Although elevated LDH showed a trend for predicting disease recurrence, it was not significant (p = 0.081; Figure 6A). However, an increase in cf-miR-210 was a significant predictor of disease recurrence (p = 0.015; Figure 6B). Akaike information criterion (AIC) values for proportional hazards regression models of cf-miR-210 was lower than that of LDH (AIC = 120.01, 122.91, respectively), which demonstrated cf-miR-210 was the better indicator of disease recurrence. Combination of cf-miR-210 and LDH did not significantly improve performance for prediction of melanoma recurrence (AIC = 120.03).


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 change in baseline LDH vs change in cf-miR-210 dCq(A) ROC analysis was performed to determine the cutoff for LDH changes (LDH Cutoff: 1.175-fold change from baseline; AUC = 0.535). Change in LDH level did not predict recurrence (  p = 0.810, AIU = 122.91) (A), while change in cf-miR-210 was a significant predictor of recurrence (B) (  p = 0.15, AIU = 120.01). Positive: Recurrence < 2 yrs, Negative: No recurrence > 5 yrs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Comparison of change in baseline LDH vs change in cf-miR-210 dCq(A) ROC analysis was performed to determine the cutoff for LDH changes (LDH Cutoff: 1.175-fold change from baseline; AUC = 0.535). Change in LDH level did not predict recurrence (  p = 0.810, AIU = 122.91) (A), while change in cf-miR-210 was a significant predictor of recurrence (B) (  p = 0.15, AIU = 120.01). Positive: Recurrence < 2 yrs, Negative: No recurrence > 5 yrs.
Mentions: LDH levels of the recurrent patients in blood were also analyzed. It was from either the same day or < 30 days of the plasma for which cf-miR-210 was assessed. Although elevated LDH showed a trend for predicting disease recurrence, it was not significant (p = 0.081; Figure 6A). However, an increase in cf-miR-210 was a significant predictor of disease recurrence (p = 0.015; Figure 6B). Akaike information criterion (AIC) values for proportional hazards regression models of cf-miR-210 was lower than that of LDH (AIC = 120.01, 122.91, respectively), which demonstrated cf-miR-210 was the better indicator of disease recurrence. Combination of cf-miR-210 and LDH did not significantly improve performance for prediction of melanoma recurrence (AIC = 120.03).

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