Transcriptomic Analysis Reveals Intrinsic Abnormalities in Endometrial Polyps

Abstract

Endometrial polyps (EPs) are benign overgrowths of the endometrial tissue lining the uterus, often causing abnormal bleeding or infertility. This study analyzed gene expression differences between EPs and adjacent endometrial tissue to elucidate intrinsic abnormalities promoting pathological overgrowth. RNA sequencing of 12 pairs of EPs and the surrounding endometrial tissue from infertile women revealed 322 differentially expressed genes. Protein-protein interaction network analysis revealed significant alterations in specific signaling pathways, notably Wnt signaling and vascular smooth muscle regulation, suggesting these pathways play critical roles in the pathophysiology of EPs. Wnt-related genes DKK1 and DKKL1 were upregulated, while GPC3, GREM1, RSPO3, SFRP5, and WNT10B were downregulated. Relevant genes for vascular smooth muscle contraction were nearly all downregulated in EPs, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN. Overall, the results indicate fundamental gene expression changes promote EP formation through unrestrained growth signaling and vascular defects. The intrinsic signaling abnormalities likely contribute to clinical symptoms of abnormal uterine bleeding and infertility common in EP patients. This analysis provides molecular insights into abnormal endometrial overgrowth to guide improved diagnostic and therapeutic approaches for this troublesome women's health condition. Confirmation of expanded cohorts and further investigations into implicated regulatory relationships are warranted.

Keywords: Wnt signaling pathway; endometrial polyps; female infertility; gene expression; vascular smooth muscle.

Figure 1

Differences in gene expression between polyps and adjacent endometrial tissues. (a) PCA analysis shows gene expression differences between polyp and control groups: red dots represent adjacent endometrial tissues (control, C) and blue dots represent polyp tissues (P). To increase the clarity of the figure, we redrew it based on the original figure. Please see Figure S1 in the Supplementary Materials for the original figure. (b) Volcano plot revealing transcriptional changes (fold change, FC = polyp/control) in polyp tissues and control groups. DEGs were defined as log_1.5 FC > 1 or < −1 with a p-value < 0.05. (c) Unsupervised hierarchical clustering heatmap of 322 DEGs. The color depth of red blocks represents the overexpression level of genes. The color depth of blue blocks represents the downregulation level of genes. (d) Expression differences (fold changes) of 10 selected genes between polyps and adjacent endometrial tissues were analyzed by qRT-PCR (green dots) and compared with RNA-seq results (blue dots) (n = 12).

Figure 2

Three PPI subclusters are shown using k-means clustering, represented by three different colors. Subclusters one, two, and three are defined by blue, red, green, with 48, 73, and 51 DEGs, respectively.

Figure 3

Cytoscape reconstruction and KEGG pathway analysis for the three PPI subclusters. Cytoscape was used to reconstruct individual PPI subclusters one to three ((a,c,e), respectively); KEGG pathway analysis reveals the significant pathways involved in each protein subcluster (b,d,f).

Figure 4

Unsupervised hierarchical clustering heatmap of Wnt signaling pathway (a) and muscle function-related genes (b).