Abstract
BACKGROUND: Serum carcinoembryonic antigen (CEA) has potential prognostic and monitoring significance in lung adenocarcinoma (LUAD) patients undergoing different treatments, such as epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy. The changes in CEA expression during relapses, influenced by resistance mechanisms involving cytokines and epigenetic factors, may impact its utility in disease prognosis, monitoring, and management. METHODS: This retrospective study analyzed advanced LUAD patients treated between 2011 and 2018, including 182 patients receiving EGFR-TKIs and 102 undergoing chemotherapies. Serum CEA levels were measured at baseline and relapse. Associations between CEA levels, treatment modalities, and survival outcomes were assessed using Cox regression and Kaplan-Meier analyses. Gene expression profiling and in vitro experiments explored the regulation of CEACAM5 expression by cytokines and epigenetic mechanisms in EGFR-TKI-resistant cells. RESULTS: Elevated baseline CEA (≥ 5 ng/mL) was associated with significantly worse overall survival (OS) in patients treated with EGFR-TKIs but showed no prognostic value in chemotherapy-treated patients. During the relapse, EGFR-TKI-treated patients were more likely to exhibit a transition to CEA-negative status (< 5 ng/mL) compared to those receiving chemotherapy. Mechanistic studies revealed that EGFR-TKI-resistant cells displayed reduced CEACAM5 expression and increased epithelial-to-mesenchymal transition (EMT) markers, driven by cytokine signaling and epigenetic modifications. CONCLUSIONS: Serum CEA is a stronger prognostic biomarker for LUAD patients treated with EGFR-TKIs while offering consistent monitoring capabilities in chemotherapy-treated patients. These findings highlight the differential clinical value of serum CEA in guiding therapeutic strategies and monitoring disease progression across treatment modalities.