Plasma circulating cell-free MYCN gene: a noninvasive and prominent
recurrence monitoring indicator of neuroblastoma
The postoperative recurrence of neuroblastoma (NB) patients is an
essential reason for the high mortality of NB due to the lack of early,
non-invasive, and dynamic strategies for monitoring NB recurrence.
Therefore, whether the plasma circulating cell-free MYCN gene as an
indicator for monitoring of NB recurrence was systematically evaluated.
The MYCN copy number and NAGK (reference gene) copy number ratio (M/N)
in plasma and corresponding tumor tissues of NB patients was detected
using an economical, sensitive and specific single-tube dual RT-PCR
approach developed in this study. The plasma M/N ratio of the MYCN gene
amplification (MNA) group (N = 25, median M/N ratio = 4.90) was
significantly higher than that of the non-MNA group (N = 71, median M/N
ratio = 1.22), P < 0.001. The M/N ratio in NB plasma (N = 60)
was positively correlated with the M/N ratio in NB tumor tissue (N =
60), with a correlation coefficient of 0.9496. In particular, the
results of dynamic monitoring of postoperative plasma M/N ratio of NB
patients showed that an abnormal increase in M/N ratio could be detected
1-2 months before recurrence in NB patients. In summary, the single-tube
double RT-PCR approache can be used to quantitatively detect MYCN copy
number. The copy number of MYCN in the tissue and plasma of NB patients
is consistent with each other. More importantly, the circulating
cell-free MYCN gene of NB patients can be used as a monitoring indicator
for early, non-invasive, and dynamic monitoring of NB recurrence.