Abstract
Changes in expression patterns of serum carcinoembryonic antigen at initial diagnosis (CEAIn) and disease progression (CEAPd) in lung cancer patients under EGFR-tyrosine kinase inhibitors (TKI) treatment may reflect different tumor progression profiles. Of the 1736 lung cancer patients identified from the cancer registry group between 2011 to 2016, we selected 517 patients with advanced stage adenocarcinoma, data on EGFR mutation status and CEAIn, among whom were 288 patients with data on CEAPd, eligible for inclusion in the correlation analysis of clinical characteristics and survival. Multivariable analysis revealed that CEAIn expression was associated with poor progression-free survival in patients harboring mutant EGFR. Moreover, CEAIn and CEAPd were associated with the good and poor post-progression survival, respectively, in the EGFR-mutant group. Cell line experiments revealed that CEA expression and cancer dissemination can be affected by EGFR-TKI selection. EGFR-mutant patients, exhibiting high CEAIn (≥5 ng/mL) and low CEAPd (<5 ng/mL), showed a potential toward displaying new metastasis. Taken together, these findings support the conclusion that EGFR mutation status is a critical factor in determining prognostic potential of CEAIn and CEAPd in patients under EGFR-TKI treatment, and CEAIn and CEAPd are associated with distinct cancer progression profiles.
Highlights
Carcinoembryonic antigen (CEA) is one of the most commonly used tumor markers whose overexpression was first discovered in colorectal cancer and followed by cancers in the aerodigestive tract and other organs[1,2]
Whether epidermal growth factor receptor (EGFR) mutation status and EGFR-tyrosine kinase inhibitors (TKI) treatment affect the prognostic potential of CEA, both before and after disease progression, remains less understood
We demonstrate that CEA levels at initial diagnosis (CEAIn) is a prognostic factor associated with poor progression-free survival (PFS) and overall survival (OS) in patients harboring EGFR mutations but not in those with wild-type EGFR
Summary
Carcinoembryonic antigen (CEA) is one of the most commonly used tumor markers whose overexpression was first discovered in colorectal cancer and followed by cancers in the aerodigestive tract and other organs[1,2]. Serum CEA is used as a marker along with imaging for monitoring tumor progression and predicting survival outcomes in colorectal cancer[3,4]. The utility of CEA as a predictive or prognostic marker of EGFR-TKI treatment response remains controversial. Several studies have reported that serum CEA levels are closely associated with EGFR-TKI treatment outcomes, and that high CEA expression after EGFR-TKI treatment predicts poor survival in patients with EGFR-mutant lung cancer[19,20]. This study aimed to further our understanding of CEA expression in different pathological subtypes in advanced lung cancer patients and to verify the effects of EGFR mutation status on the prognostic potential of CEA in these patients. CEA levels at initial diagnosis (CEAIn) and at disease progression (CEAPd) were extracted to study the association between CEA heterogeneity, metastasis and remaining survival after disease progression in these patients. We used EGFR-mutant lung adenocarcinoma cells to monitor the change of CEA heterogeneity after EGFR-TKI treatment and its association with dissemination and chemoresistant properties of lung cancer cells
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