Tissue-, Blood-, and Urine-Based Proteomics Changes of Different Endometrial Receptivity Status in Patients after Fertility-Sparing Treatment of Atypical Endometrial Hyperplasia or Endometrial Cancer

Liquid biopsy noninvasively characterizes diseases by analyzing biomarker proteins in biofluids, which provide valuable insights into physiological and pathological processes. In this study, we conducted an analysis of the differences between atypical endometrial hyperplasia or endometrial cancer (AH/EC) patients after fertility-sparing treatment with different RNA-Seq-based endometrial receptivity test (rsERT) results ("receptive" versus "pre-receptive"), to investigate the proteomic connections among tissue, serum, and urine samples. Samples of endometrial tissue, serum, and urine from 40 rsERT "pre-receptive" and 10 rsERT "receptive" patients were analyzed for proteomic profiling. We integrated differentially expressed proteins from three sample types to investigate endometrial receptor (ER)-related molecular changes. Our findings indicated that both serum and urine proteomes can serve as indicators of functional changes in endometrial tissue. In serum, proteins associated with cholesterol metabolism, immune response, and coagulation exhibited a differential expression. In urine, proteins related to immune function and metabolic processes demonstrated varying levels of expression. The differentially expressed proteins in both serum and urine were associated with the immune response and metabolism. In conclusion, biofluids serve as a reflection of functional changes in endometrial tissue, which will facilitate a deeper understanding of endometrial receptivity and the discovery of potential clinical biomarkers.