Integrated Analysis Identifies Four Genes as Novel Diagnostic Biomarkers Which Correlate with Immune Infiltration in Preeclampsia

Abstract

Preeclampsia remains a high cause of incidence and death for mothers and fetuses in developing nations. Preeclampsia has numerous clinical and biochemical markers that have been tested, but they have failed to provide a conclusive diagnosis in the different phases of the disease’s progression. Herein, our team intended to determine potential diagnostic biomarkers for preeclampsia and analyzed associations with immune cells. Two microarray data from mankind’s preeclampsia and control specimens were acquired from GSE75010 and GSE44711 datasets. Differentially expressed genes (DEGs) were identified between77 normal samples and 80 preeclampsia samples. Candidate biomarkers were discovered using the least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) analysis. The expressions and diagnostic values of genes in preeclampsia were further demonstrated in the GSE44711 dataset (8 control samples and 8 preeclampsia samples). The correlation of critical genes with the proportion of immune cells was analyzed. We identified 20 DEGs in preeclampsia. Diseases enriched by DEGs were mainly related to preeclampsia, gestational diabetes, ovarian disease, female reproductive system disease, and endocrine system disease. COL17A1, FLT1, FSTL3, and SERPINA3 were identified as diagnostic genes of preeclampsia and validated in the GSE44711 datasets. Immune cell infiltration assays suggested that COL17A1, FLT1, FSTL3, and SERPINA3 were related to several immune cells. Overall, we identified four critical diagnostic genes in preeclampsia. Furthermore, more well-designed research studies with larger cohorts were warranted to confirm the value of the four genes for the diagnosis and outcome of preeclampsia patients.

A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia

“…It suggests a potential link between the deregulation of extracellular matrix interactions and the development of PE. Moreover, our findings align with prior research that COL17A1 is differentially expressed in PE ( 25 ). COL17A1 protein can be detected in urine samples from pregnant patients, but differential expression in terms of PE compared to NP has not been thoroughly investigated ( 26 ).…”

Comparison of immune‐related gene signatures and immune infiltration features in early‐ and late‐onset preeclampsia

“…Recent genome-wide association researches and immunological studies have focused on the correlation between immune maladaptation and preeclampsia. [24][25][26] However, the different pathogenesis of the main two preeclampsia subtypes, EOPE and LOPE, is usually ignored. The placental immune process is crucial for maintaining a tolerogenic environment and the development of the placenta and fetus.…”

“…Despite the understanding of preeclampsia becoming clear with more and more studies on the mechanism, there are still numerous key questions waiting to be answered. Recent genome‐wide association researches and immunological studies have focused on the correlation between immune maladaptation and preeclampsia 24–26 . However, the different pathogenesis of the main two preeclampsia subtypes, EOPE and LOPE, is usually ignored.…”

Detection and assessment of immune and stromal related risk genes to predict preeclampsia: A bioinformatics analysis with dataset

“…This mechanism involves enhancing placental lipid storage in PE patients. [41] However, the expression and mechanisms of COL17A1 and SH3BP5 have not been investigated. BHLHE40 is a transcriptional repressor in response to hypoxia.…”