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Background:We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods.Methods:We enrolled 50 patients with EM,34 with benign ovarian neoplasms and 40 healthy volunteers in this study.Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads.Possible biomarkers were analyzed by a random and repeat patt model-validation method that we designed,and ClinProtools software,results were refined using online liquid chromatography-tandem MS.Results:We found a cluster of 5 peptides (4210,5264,2660,5635,and 5904 Da),using 3 peptides (4210,5904,2660 Da) to discriminate EM patients from healthy volunteers,with 96.67％ sensitivity and 100％ specificity.We selected 4210 and 5904 m/z,which differed most between patients with EM and controls,and identified them as fragments of ATP1B4,and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor,respectively.Conclusions:ClinProt can identify EM biomarkers,which-most notably-distinguish even early-stage or minimal disease.We found 5 stable peaks at 4210,5264,2660,5635,and 5904 Da as potential EM biomarkers,the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.