Four microRNAs as Prognostic Biomarkers for Overall Survival in Uterine Carcinosarcoma

Abstract—Uterine carcinosarcoma (UCS) is a rare, biphasic,
and highly aggressive gynecologic malignancy with disproportionately poor prognosis. Although microRNAs (miRNAs) regulate
tumorigenesis across many cancers, their prognostic role in
UCS remains largely undefined, owing to the rarity of the
disease and the scarcity of matched expression-plus-survival
cohorts. We sought to derive and internally validate an miRNAbased prognostic signature for overall survival in UCS using
public data. miRNA and mRNA expression and clinical data
for 55 UCS patients (34 deaths, 62%) were obtained from The
Cancer Genome Atlas (TCGA). As weighted correlation network
analysis identified no survival-associated module, we adopted a
direct approach: univariate Cox regression screened survivalassociated miRNAs, and a signature was built by LASSO Cox
regression with the number of miRNAs optimized by repeated
cross-validation. A four-miRNA signature (hsa-miR-1249, hsamiR-1287, hsa-miR-30d, hsa-miR-330) was identified. High-risk
patients had significantly shorter overall survival than low-risk
patients (log-rank P = 6.67 × 10−5). Time-dependent AUCs
were 0.79, 0.74, and 0.76 at 1, 2, and 3 years; repeated 70/30
cross-validation gave a more conservative mean test AUC of 0.69
(95% range 0.41–0.84). The risk score remained an independent
prognostic factor after adjustment for age and stage (hazard ratio
= 2.72, P = 1.67×10−6). Enrichment of correlated target genes
highlighted hypoxia and peptide-hormone responses. This compact signature provides moderate, independent prognostic value
for UCS and may serve as a hypothesis-generating biomarker;
given the small single-cohort sample, external and experimental
validation are required.