Integrated Analysis of Microbiome and Transcriptome Data Reveals the Interplay Between Commensal Bacteria and Fibrin Degradation in Endometrial Cancer

Abstract

The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. We found that Pelomonas and Prevotella were enriched in the EC group with a high tumor burden. By integrating the microbiome and hematological indicators, a correlation was observed between Prevotella and elevated serum D-dimer (DD) and fibrin degradation products (FDPs). Further transcriptome analysis identified 8 robust associations between Prevotella and fibrin degradation-related genes expressed within ECs. Finally, the microbial marker of Prevotella along with DD and FDPs showed a high potential to predict the onset of EC (AUC = 0.86). Our results suggest that the increasing abundance of Prevotella in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden. The microbe-associated transcripts of host tumors can partly explain how Prevotella promotes DD and FDPs.

Current findings in endometrial microbiome: impact on uterine diseases

“…Hence, Prevotella may promote fibrin degradation by inducing the expression of specific genes. Moreover, the authors propose that their identity could be used to predict or diagnose endometrial cancer (Li et al 2021).…”

The Role of Microbiota in the Immunopathogenesis of Endometrial Cancer

“…As shown by other studies available in the literature, Porphyromonas sp. have previously been isolated intracellularly, and it is possible that they are capable of interfering with normal cellular regulatory processes and, thus, triggering the process of carcinogenesis [ 60 , 61 , 62 ].…”

“…in endometrial lesions may play a putative role in the development of endometrial cancer [ 43 ]. Moreover, the team of Li et al in 2021, showed that the advanced severity of the disease is associated with a reduction in the diversity of the endometrial microbiome [ 62 ]. After completing their transcriptome research, they found altered expression of genes associated with fibrin breakdown in endometrial tumor tissues.…”

“…After completing their transcriptome research, they found altered expression of genes associated with fibrin breakdown in endometrial tumor tissues. Further correlation analysis showed that these genes were associated with an increase in the abundance of Prevotella sp., indicating that Prevotella may play a key role in mediating host fibrin breakdown leading to EC [ 62 ].…”

“Iron triangle” of regulating the uterine microecology: Endometrial microbiota, immunity and endometrium

“…Li et al. reported that the proportions of Prevotella, Muribaculum Pelomonas and Nocardioides in EC patients were higher than those in healthy people, while the proportion of Oscillibacter was lower ( 170 ). Walther-antonio et al.…”