Abstract
OBJECTIVE: Ovarian cancer is one of the most lethal gynecological malignancies, with high recurrence rates and poor prognosis. Identifying molecular mechanisms underlying recurrence is critical for improving patient outcomes. This study aimed to develop a recurrence-related gene signature (RRGS) for prognosis and explore the role of Myeloid/Lymphoid or Mixed-Lineage Leukemia; Translocated To 6 (MLLT6), a key gene within the RRGS, in ovarian cancer progression and drug resistance. METHODS: TCGA and GEO cohorts were analyzed to identify differentially expressed genes (DEGs) associated with recurrence. LASSO regression was applied to construct an eight-gene RRGS, which was validated in independent cohorts. Functional assays, including proliferation, migration, invasion, and drug resistance tests, were conducted in OVCAR3, TOV-21G and ES-2 cell lines to evaluate the role of MLLT6. RESULTS: The RRGS effectively stratified patients into high- and low-risk groups, with high RRGS scores correlating with poorer overall survival and progression-free survival. Among the RRGS genes, MLLT6 was identified as the most significant prognostic marker. Functional assays showed that MLLT6 knockdown inhibited ovarian cancer cell proliferation, migration, invasion, and significantly enhanced Paclitaxel sensitivity by reducing IC50 values. CONCLUSION: The RRGS is a robust prognostic tool for ovarian cancer, and MLLT6 plays a critical role in tumor progression and drug resistance. Targeting MLLT6 may provide a novel therapeutic strategy to overcome Paclitaxel resistance and improve patient outcomes.