Diagnostic value of the iron apoptosis-related gene in recurrent miscarriage

The early diagnosis and treatment of recurrent miscarriage are essential for preventing adverse pregnancy outcomes. This study explores the value of iron apoptosis-related gene in the diagnosis of recurrent pregnancy loss (RPL).

We obtained ferroptosis-related differentially expressed genes (DEGs) associated with RPL from the GEO database and the FerrDb database. Ferroptosis-related DEGs were subjected to functional analysis and protein-protein interaction analysis to obtain hub genes. A functional analysis of ferroptosis-related DEGs was performed. A protein-protein interaction network was used to identify the hub genes. In vitro experiments were used to verify their diagnostic value for RPL in our hospital. In addition, the online software Network Analyst was used to obtain miRNAs associated with core genes, and the immune landscape was explored in RPL patients and controls.

In total, 2245 DEGs were obtained from the GSE26787 dataset, of which 51 were ferroptosis-related DEGs. The top 4 genes are KRAS, SRC, EGFR, and MDM2. In the training set GSE26787, only SRC was significantly upregulated in the RSA group compared with the control group, with an area under the curve of 0.92. In the validation set GSE165004, 3 genes (EGFR, KRAS, SRC) were differentially expressed, with areas under the curve of 0.776, 0.964, and 0.814, respectively. Our serum samples revealed a statistically significant difference in KRAS expression in the RPL group only, with an area under the curve of 0.77. miR-1-3p and miR-155-5p interact with all 4 ferroptosis-related DEGs.

The iron apoptosis-related genes such as EGFR, KRAS, SRC, and MDM2 are valuable for the early diagnosis of recurrent miscarriage. They affect the hypoxia of the endometrium during the implantation period through the FoxO signaling pathway, leading to a reduction in the number and volume of microvessels, which in turn causes recurrent miscarriage.