Abstract
Objectives
MicroRNAs
(miRNAs) are a class of small non-coding RNAs that negatively regulate
gene expression primarily through post-transcriptional modification. We
tested the hypothesis that miRNA expression is associated with overall
survival in advanced ovarian cancer.
Results
Of
all patients, 80% had high-grade, stage IIIC tumors and 64% underwent
optimal cytoreduction. The median survival for the entire cohort was
49 ± 4 months. The training set identified 3 miRNAs associated with
survival —
miR-337,
miR-410, and
miR-645. An miRNA signature containing
miR-410 and
miR-645
was most strongly associated with overall survival in the training set
(HR = 2.96, 95% CI: 1.51–5.78). This miRNA survival signature (MiSS) was
validated in the test set (HR = 1.71, 95% CI: 1.05–2.78).
The MiSS was
independent of FIGO stage and surgical debulking.
Conclusions
The data suggest that an MiSS that contains
miR-410 and
miR-645
is negatively associated with overall survival in advanced
serous
ovarian cancer. This signature, when further validated, may be useful in
individualizing care for the ovarian cancer patient. Pathway analyses
identify biologically plausible mechanisms.
Research highlights
► A
MicroRNA Survival Signature was developed in advanced ovarian carcinoma.
► The signature was independent of common clinical co-variates.
