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abstract
Background: Ovarian
cancer is the leading cause of death among malignancies in women.
Despite advances in treatment, >50% of patients
relapse. For disease monitoring, the
identification of a blood-based biomarker would be of prime interest. In
this regard,
noncoding RNAs, such as microRNA (miRNA) or
small nuclear RNA (snRNA), have been suggested as biomarkers for
noninvasive cancer
diagnosis. In the present study, we sought to
identify differentially expressed miRNA/snRNA in sera of ovarian cancer
patients
and investigate their potential to aid in
therapy monitoring.
Methods: miRNA/snRNA abundance was investigated in serum (n = 10) by microarray analysis and validated in an extended serum set (n
= 119) by reverse-transcription quantitative PCR.
Results: Abundance of U2-1 snRNA fragments (RNU2-1f) was significantly increased in sera of ovarian cancer patients (P < 0.0001) and paralleled International Federation of Gynecology and Obstetrics stage as well as residual tumor burden after
surgery (P < 0.0001 and P = 0.011, respectively). Moreover, for patients with suboptimal debulking, preoperative RNU2-1f concentration was associated
with radiographic response after chemotherapy and with platinum resistance (P = 0.0088 and P
= 0.0015, respectively). Interestingly, according to the RNU2-1f
abundance dynamics, persistent RNU2-1f positivity before
surgery and after chemotherapy identified a
subgroup of patients with high risk of recurrence and poor prognosis.
Conclusions: This is
the first report to suggest that a circulating snRNA can serve as an
auxiliary diagnostic tool for monitoring tumor
dynamics in ovarian cancer. Our results provide a
rationale to further investigate whether this high-risk patient group
may
benefit from additional therapies that are
directly applied after chemotherapy.
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