KLF2 as a prognostic and potential therapeutic target associated with ferroptosis in serous ovarian cancer: An integrative bioinformatics and clinical validation study

Abstract

Serous ovarian cancer (SOC), a prevalent histological subtype of ovarian cancer, poses a notable global threat to women's health. Ferroptosis has emerged as a pivotal focus in cancer research, presenting a promising novel therapeutic target. The present study aimed to identify key ferroptosis-related genes in SOC and evaluate their clinical implications. Gene expression profiles for SOC were obtained from the Gene Expression Omnibus database. Differential expression analysis and weighted gene co-expression network analysis, in conjunction with ferroptosis-related datasets, identified 22 differentially expressed genes associated with both SOC and ferroptosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated their involvement in critical biological processes and pathways. Protein-protein interaction (PPI) network analysis identified four central hub genes: Kruppel-like factor 2 (KLF2), fatty acid binding protein 4 (FABP4), caveolin 1 (CAV1) and α-synuclein (SNCA). Validation using The Cancer Genome Atlas (TCGA) database confirmed significant downregulation of these genes in SOC (P<0.05), with an assessment of their potential diagnostic value. Peripheral blood samples were collected from 20 patients with SOC (experimental group) and 20 healthy volunteers (control group). Reverse transcription-quantitative PCR demonstrated that KLF2 was significantly downregulated in patients with SOC (P<0.05), while FABP4, CAV1 and SNCA did not show significant differences. Consequently, subsequent experiments concentrated on KLF2. The downregulation of KLF2 was further validated using the Human Protein Atlas database. Kaplan-Meier survival analysis revealed that low KLF2 expression was associated with a poor prognosis in patients with SOC. A nomogram suggested that KLF2 could serve as a prognostic biomarker for SOC. Immune infiltration analysis was performed based on TCGA data. Finally, interaction networks for microRNA-KLF2, transcription factor-KLF2 and chemical-KLF2 were constructed to predict potential molecular mechanisms and therapeutic drugs targeting KLF2 in SOC. These findings indicate that KLF2 may serve as a prognostic and potential therapeutic target related to ferroptosis in serous ovarian cancer, warranting further investigation.