Abstract: OBJECTIVE： To investigate the mechanisms by which malonyl-CoA decarboxylase (MLYCD) regulates platinum resistance in ovarian cancer and its clinical application value. METHODS： Immunohistochemical staining (IHC) was performed on ovarian cancer tissue microarrays to validate MLYCD expression levels in patients with varying platinum sensitivities. Using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) databases， protein and mRNA expression levels of MLYCD among these patients were evaluated and their association with clinical characteristics was examined. The pRRophetic algorithm was used to evaluate sensitivity of the samples to cisplatin. Proteins significantly correlated with MLYCD expression were selected to construct a protein-protein interaction (PPI) network，and the GEPIA2 database was used to retrieve MLYCD-related genes at the transcriptome level. Related signaling pathways were enriched using the KEGG and GO methods. The immune infiltration status of patients' tumor tissues was evaluated using the Estimate algorithm，tumor immune dysfunction and exclusion (TIDE) score，and Immunophenoscore (IPS). Western blot (WB) was used to validate the expression of MLYCD protein in cisplatin-sensitive/resistant ovarian cancer cell lines. RESULTS： The tissue microarray IHC results， together with CPTAC data， showed that MLYCD expression was higher in platinum-resistant patients than in platinum-sensitive patients and exhibited an increasing trend with tumor substage progression (P=0.046). Both CPTAC and TCGA data indicated that MLYCD expression was positively correlated with cisplatin resistance (r> 0.3， P<0.05). Furthermore， MLYCD and its interacting proteins were mainly involved in metabolic reprogramming that promoted lipid catabolism. The Estimate，TIDE，and IPS scores indicated that，compared to the low-expression group， ovarian tumors with high MLYCD expression harbored greater infiltration of dysfunctional immune cells and exhibited reduced antitumor activity. Western blot experiments further confirmed a significant increase in MLYCD expression in platinum-resistant ovarian cancer cell lines (P<0.05). CONCLUSION： MLYCD was highly expressed in platinum-resistant ovarian cancer tissues and participated in metabolic reprogramming toward lipid catabolism to supply energy for ovarian cancer cells. Thus，MLYCD may serve as a biomarker for platinum resistance and a potential therapeutic target in ovarian cancer.

Key words: ovary neoplasms, platinum resistance, malonyl-CoA decarboxylase, immune microenvironment