A Pseudo-Targeted Metabolomics Study Based On Serum Bile Acids Profiling For The Differential Diagnosis Of Benign And Malignant Breast Lesions

Introduction: Breast cancer (BC) has become the most commonly diagnosed cancer worldwide. It is very critical for the differential diagnosis between BC and benign breast diseases (BBD). The characteristics of serum bile acids (BAs) profiling in patients with BBD and BC was elucidated so that potential biomarkers could be find out for the differential diagnosis of BC and BBD. Methods: A pseudo-targeted approach was used to perform BAs metabolomics analysis in serum of 29 patients with BBD and 47 patients with BC by ultra-high performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Partial least squares-discriminant analysis (PLS-DA) was used to establish a differential diagnostic model for BC, and the receiver operating characteristic (ROC) curve and logistic regression analysis were used to screen out bile acids as biomarkers for the differential diagnosis of BC and BBD. Results: The serum BAs profile in BC group was quite different from that in BBD group. Compared with the BBD group, BC group had higher level of chenodeoxycholic acid (CDCA), while they had lower levels of dihydroxy tauro-conjugated BA (Tdi-1) and sulfated dihydroxy glyco-conjugated BA (Gdi-S-1). The sensitivity and specificity of PLS-DA model for patients classification were 100% and 92.3%, respectively. The combined biomarker, CDCA and Tdi-1, had high efficacy for the differential diagnosis (area under the curve was 0.954, 95% CI: 0.8801.000) of BC. Besides, the performance was superior to traditional biomarkers in the differential diagnosis of BC with or without comorbidities. Conclusion: The profile of serum BAs in women with BC was quite different from that in patients with BBD. Serum BAs profiling analysis could be used as an effective tool for the differential diagnosis of BC and BBD.