Integrated proteomic and lipidomic analysis revealed potential plasma biomarkers for cervical cancer

Abstract

Cervical cancer (CC) remains the most prevalent malignant tumor in the female reproductive system. However, the absence of specific biomarkers and typical clinical manifestations in the early stages significantly impedes early diagnosis, prevention, and treatment efforts. Sensitive, non-invasive biomarkers are urgently necessary for the early detection of CC. This study leveraged proteomic and lipidomic analyses on plasma samples from 115 high-grade squamous intraepithelial lesion (HSIL) patients, 133 CC patients, and 88 healthy controls (CT) and develops robust models for effectively predicting CC. Proteomic profiles revealed 48 differentially abundant proteins in HSIL and CC patients, respectively, most of which were duplicated in two patient groups. HSIL displayed specific lipid accumulation in both discovery and validation cohorts. The elevated lipids were enriched in triglycerides (TG) and phosphatidylcholines (PC), while the lower lipids were enriched in fatty acids (FA). Random Forest classifier results suggest that 4 CC-specific plasma proteins [fibrinogen, complement C3 (C3), hemoglobin subunit alpha, alpha-1-antitrypsin (SERPINA1)], 2 of which were core lipid-interacted proteins (C3, SERPINA1), show predictive ability for CC in both discovery and validation cohorts (AUC 0.97 and 0.64). Our results suggest that lipid and protein perturbations exhibit differential sensitivity towards HSIL and CC and may be used as non-invasive diagnostic markers.