Association of Divergent Carcinoembryonic Antigen Patterns and Lung Cancer Progression

Abstract

changes in expression patterns of serum carcinoembryonic antigen at initial diagnosis (ceA in) and disease progression (ceA pd) 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 ceA in , among whom were 288 patients with data on ceA pd , eligible for inclusion in the correlation analysis of clinical characteristics and survival. Multivariable analysis revealed that ceA in expression was associated with poor progression-free survival in patients harboring mutant EGFR. Moreover, CEA in and ceA pd 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 ceA in (≥5 ng/mL) and low CEA pd (<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 ceA in and ceA pd in patients under eGfR-tKi treatment, and ceA in and ceA pd are associated with distinct cancer progression profiles. 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. Although the suitability of CEA as an effective marker for lung cancer remains debatable, characteristics such as lower cost, noninvasiveness, and lack of other reliable markers, make CEA an attractive option in lung cancer 5,6. Additionally, CEA measurements before and after surgery have been suggested to provide valuable information for predicting disease progression and for determining the need for adjuvant treatment during early stage lung cancer 7,8. As proven by several large-scale clinical trials, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) are highly effective in lung cancer patients harboring EGFR activating mutations, mainly, deletions in exon 19 (Del19) and a L858R mutation in exon 21 9-13. However, despite an initial positive response, patients harboring the activating EGFR mutations ultimately develop resistance to EGFR-TKI by different mechanisms 14-18. Thus, 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. In contrast, some reports have shown that CEA levels...

Early identification of disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis

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