Identification and analysis of biomarkers associated with oxidative stress and ferroptosis in recurrent miscarriage.

ABSTRACT

Recurrent miscarriage (RM) has a huge impact on women. Both oxidative stress and ferroptosis play an important role in the pathogenesis of RM. Hence, it was vital to screen the ferroptosis oxidation-related biomarkers for the diagnosis and treatment of RM. We introduced transcript data to screen out differentially expressed genes (DEGs) in RM. Ferroptosis oxidation-related differentially expressed genes were obtained by overlapping DEGs and oxidative stress related genes with correlations >0.9 with ferroptosis-related genes. Least Absolute Shrinkage and Selectionator operator regression and support vector machine based recursive feature elimination algorithm were implemented to screen feature genes. The biomarkers associated with ferroptosis oxidation were screened via receiver operating characteristic curve analysis. We finally analyzed the competing endogenous RNAs regulatory network and potential drugs of biomarkers. We identified 1047 DEGs in RM. Then, 9 ferroptosis oxidation-related differentially expressed genes were obtained via venn diagram. Subsequently, 8 feature genes (PTPN6, GJA1, HMOX1, CPT1A, CREB3L1, SNCA, EPAS1, and TGM2) were identified via machine learning. Moreover, 4 biomarkers associated with ferroptosis oxidation, including PTPN6, GJA1, CPT1A, and CREB3L1, were screened via receiver operating characteristic curve analysis. We constructed the '227 long noncoding RNAs-4 mRNAs-36 microRNAs' network, in which hsa-miR-635 was associated with CREB3L1 and PTPN6. There were 11 drugs with therapeutic potential on 3 biomarkers associated with ferroptosis oxidation. We also observed higher expression of CPT1A and CREB3L1 in RM group compared to the healthy control group by quantitative real-time reverse transcription polymerase chain reaction. Overall, we obtained 4 biomarkers (PTPN6, GJA1, CPT1A, and CREB3L1) associated with ferroptosis and oxidative stress, which laid a theoretical foundation for the diagnosis and treatment of RM.