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

Chao Li,Ye Gu,Yunfeng Song,Xiaoping Wan,Qizhi He,Yiran Li,Jian Huang

doi:10.3389/fcimb.2021.748558

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.

Highlights

Endometrial cancer (EC) is the most common female reproductive tract malignancy in developed countries and shows an increasing incidence (Bray et al, 2018)
Symptoms of endometrial cancer (EC), such as abnormal vaginal bleeding, usually present quickly after cancer onset, and most EC patients are diagnosed at an early stage
We provided evidence that the tumor burden is associated with the presence of specific endometrial microbiota, which is distinguished by the enrichment of Pelomonas and Prevotella in patients with EC

Summary

Introduction

Endometrial cancer (EC) is the most common female reproductive tract malignancy in developed countries and shows an increasing incidence (Bray et al, 2018). Prevotella Mediates Endometrial Cancer Occurrence to play important roles in endometrial carcinogenesis, they can only explain 10–20% of cases (Walther-António et al, 2016; Kuźmycz and Staczek, 2020). Efforts to identify the cause of the remaining 80–90% of cases have led to studies on a number of environmental factors, including hormones, obesity, inflammation, and menopausal status, which are major risk factors for the development of type I EC (Beral et al, 2005; Morice et al, 2016). There is an urgent need to identify previously unrecognized mechanisms for the diagnosis and therapeutic management of EC. The underlying mechanisms involved in the occurrence and development of EC are far from being explored

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