Transcriptomic Profiling Reveals Predictive Markers of Response to Concurrent Chemoradiotherapy plus Immune Checkpoint Inhibition in Cervical Cancer

Background Concurrent chemoradiotherapy (CCRT) combined with immune checkpoint inhibition has emerged as a promising treatment for locally advanced cervical cancer (LACC), yet approximately 30% of patients fail to achieve complete response. Methods Here, we performed RNA sequencing on pretreatment biopsies from 71 LACC patients treated with CCRT plus toripalimab to identify transcriptomic signatures associated with treatment response. Results We found 21 genes upregulated in complete responders (CR) and 133 genes upregulated in non-complete responders (non-CR) (|log2FoldChange|≥1, P < 0.05). Pathway analysis revealed enrichment of B-cell signaling in CR tumors and neutrophil-related pathways in non-CR tumors. A three-gene prognostic model (BCAT1, ITGA5, CXCL2) demonstrated robust performance in predicting overall survival in both training (AUC = 0.82) and validation cohorts (AUC = 0.79). Single-cell RNA sequencing showed predominant expression of these genes in myeloid and endothelial cells. Non-CR tumors exhibited elevated expression of immune checkpoint genes, suggesting potential benefit from combination therapy. Conclusions These findings provide insights into resistance mechanisms and may guide personalized chemo-radio-immunotherapy strategies for LACC.