Plasma Proteomic Biomarkers for Predicting Chemoradiation Response in Locally Advanced Cervical Cancer

ABSTRACT: A significant proportion of patients with locally advanced cervical cancer (LACC) experience treatment failure following concurrent chemoradiation therapy (CRT). Identifying patients unlikely to respond to CRT could inform personalized treatment strategies. In this study, we evaluated plasma proteomic profiles in 39 LACC patients stratified by CRT response: complete response (CR), partial response (PR), and progressive disease (PD). Using nano-liquid chromatography tandem mass spectrometry with data-independent acquisition (nano-LC MS/MS-DIA), we identified 507 protein groups, of which 407 were consistently detected in more than 50% of samples. Differential expression analysis revealed eight proteins significantly downregulated in non-responders, all of which are involved in inflammatory response pathways. Further subclass analysis demonstrated distinct proteomic dysregulation in PR patients compared to both CR and PD groups, with enrichment of pathways related to complement activation, NF-κB signaling, and lipid metabolism. Targeted validation using parallel reaction monitoring (PRM) confirmed a panel of 11 proteins that robustly distinguished PR from CR, yielding an area under the curve (AUC) of 0.862 (95% CI: 0.793–0.921). Integration with tumor RNA-seq data from The Cancer Genome Atlas (TCGA) revealed coordinated dysregulation in pathways involving HIF-1 signaling, proteoglycan and choline metabolism, PI3K-Akt signaling, and the complement and coagulation cascade. These findings suggest that baseline plasma protein profiles reflect underlying systemic inflammation and metabolic status, offering potential utility in predicting CRT responsiveness in LACC.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Kittinun Leetanaporn 

PROVIDER: PXD064941 | JPOST Repository | Mon Nov 03 00:00:00 GMT 2025

REPOSITORIES: jPOST