Integrated Proteomics and Metabolomics Profiling Unveils Biomarkers and Immune Characteristics for Pelvic Lymph Node Metastasis in Cervical Cancer

Pelvic lymph node metastasis (PLNM) significantly affects the prognosis of cervical cancer (CC). However, current imaging examinations and serum squamous cell carcinoma antigen (SCCA) testing are inadequate for assessing the pelvic lymph node status in CC. To identify accurate noninvasive biomarkers for diagnosing PLNM and minimizing unnecessary postoperative lymphadenectomy and its associated complications, we performed a comprehensive proteomic and metabolomic analysis of plasma from 124 patients with CC, along with a proteomic analysis of 60 paired tissue samples. Through machine learning methods, we identified potential plasma biomarkers (TTR, MASP2, APOD, and 7α-hydroxy-cholestene-3-one) and constructed a diagnostic model. In the validation cohort, the diagnostic model combined with SCCA exhibited a higher sensitivity (72.4%) than SCCA (64.3%) and imaging examination (14.3%). The plasma protein biomarkers were consistently validated in paired tissue samples. Additionally, immune infiltration analysis demonstrated that CD4 and CD8 T cells were highly infiltrated in the PLNM group, suggesting a potentially enhanced response to immunotherapy. Here, we established a biomarker panel for PLNM and highlighted the altered immune characteristics associated with PLNM, offering valuable insights for the development of immunotherapy strategies for patients with PLNM.