Elevated serum CEA levels are associated with the explosive progression of lung adenocarcinoma harboring EGFR mutations

被引:44
作者
Gao, Yuan [1 ]
Song, PingPing [2 ,4 ]
Li, Hui [2 ]
Jia, Hui [3 ]
Zhang, BaiJiang [2 ]
机构
[1] Shandong Univ, Shandong Prov Hosp, Dept Thorac Surg, Jinan 250117, Shandong, Peoples R China
[2] Shandong Tumor Hosp & Inst, Dept Thorac Surg, Jinan 250117, Shandong, Peoples R China
[3] Shandong Tumor Hosp & Inst, Dept Med Oncol, Jinan 250117, Shandong, Peoples R China
[4] Shandong Canc Hosp & Inst, Dept Thorac Surg, Jiyan Rd 440, Jinan 250117, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Biomarker; EGFR; EGFR-TKIs; Mutation; Response; FACTOR RECEPTOR MUTATIONS; HUMAN-TUMOR-MARKER; II CLINICAL-TRIAL; CARCINOEMBRYONIC ANTIGEN; CANCER; ERLOTINIB; GEFITINIB; CHEMOTHERAPY; EXPRESSION; PLASMA;
D O I
10.1186/s12885-017-3474-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Serum carcinoembryonic antigen (CEA) levels are a predictor of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) efficacy and are associated with epidermal growth factor receptor (EGFR) gene mutations. However, the clinical significance of plasma CEA level changes during different cycles of target therapy is unknown for lung adenocarcinoma patients with sensitizing EGFR mutations. Methods: In total, 155 patients with lung adenocarcinoma were enrolled in this retrospective study between 2011 and 2015. EGFR mutations were detected by RT-PCR (real-time quantitative PCR). Plasma CEA levels were measured prior to different EGFR-TKI treatment cycles. Computed tomography (CT) scans were conducted every 2 months to assess the therapeutic efficacy. Results: Serum CEA concentrations were significantly associated with EGFR mutations (p < 0.05). Furthermore, in all patients treated with EGFR-TKIs, the serum CEA levels increased with disease progression (p < 0.005). A COX multivariate analysis revealed that CEA levels 16.2 times above normal were associated with early disease progression (HR, 5.77; 95% CI: 2.36 similar to 14.11; p < 0.001). Based on this finding, a threshold was set at the median time of 8.3 months. Patients with EGFR mutations exhibited a median progression-free survival time of 12.8 months. Serum CEA levels were markedly increased compared to levels measured 4.5 months prior to the changes detected via CT scans for patients resistant to EGFR-TKIs. Conclusions: Elevated CEA levels during targeted therapy may be a more sensitive predictor of explosive lung adenocarcinoma progression in patients harboring mutant EGFRs compared to traditional imaging methods.
引用
收藏
页数:7
相关论文
共 43 条
[1]   CARCINOEMBRYONIC ANTIGEN, A HUMAN-TUMOR MARKER, FUNCTIONS AS AN INTERCELLULAR-ADHESION MOLECULE [J].
BENCHIMOL, S ;
FUKS, A ;
JOTHY, S ;
BEAUCHEMIN, N ;
SHIROTA, K ;
STANNERS, CP .
CELL, 1989, 57 (02) :327-334
[2]   Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].
Bettegowda, Chetan ;
Sausen, Mark ;
Leary, Rebecca J. ;
Kinde, Isaac ;
Wang, Yuxuan ;
Agrawal, Nishant ;
Bartlett, Bjarne R. ;
Wang, Hao ;
Luber, Brandon ;
Alani, Rhoda M. ;
Antonarakis, Emmanuel S. ;
Azad, Nilofer S. ;
Bardelli, Alberto ;
Brem, Henry ;
Cameron, John L. ;
Lee, Clarence C. ;
Fecher, Leslie A. ;
Gallia, Gary L. ;
Gibbs, Peter ;
Le, Dung ;
Giuntoli, Robert L. ;
Goggins, Michael ;
Hogarty, Michael D. ;
Holdhoff, Matthias ;
Hong, Seung-Mo ;
Jiao, Yuchen ;
Juhl, Hartmut H. ;
Kim, Jenny J. ;
Siravegna, Giulia ;
Laheru, Daniel A. ;
Lauricella, Calogero ;
Lim, Michael ;
Lipson, Evan J. ;
Marie, Suely Kazue Nagahashi ;
Netto, George J. ;
Oliner, Kelly S. ;
Olivi, Alessandro ;
Olsson, Louise ;
Riggins, Gregory J. ;
Sartore-Bianchi, Andrea ;
Schmidt, Kerstin ;
Shih, Ie-Ming ;
Oba-Shinjo, Sueli Mieko ;
Siena, Salvatore ;
Theodorescu, Dan ;
Tie, Jeanne ;
Harkins, Timothy T. ;
Veronese, Silvio ;
Wang, Tian-Li ;
Weingart, Jon D. .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)
[3]   Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study [J].
Cappuzzo, Federico ;
Ciuleanu, Tudor ;
Stelmakh, Lilia ;
Cicenas, Saulius ;
Szczesna, Aleksandra ;
Juhasz, Erzsebet ;
Esteban, Emilio ;
Molinier, Olivier ;
Brugger, Wolfram ;
Melezinek, Ivan ;
Klingelschmitt, Gaelle ;
Klughammer, Barbara ;
Giaccone, Giuseppe .
LANCET ONCOLOGY, 2010, 11 (06) :521-529
[4]   Liquid Biopsies: Genotyping Circulating Tumor DNA [J].
Diaz, Luis A. ;
Bardelli, Alberto .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (06) :579-+
[5]   Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].
Ferlay, Jacques ;
Shin, Hai-Rim ;
Bray, Freddie ;
Forman, David ;
Mathers, Colin ;
Parkin, Donald Maxwell .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917
[6]   Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA [J].
Forshew, Tim ;
Murtaza, Muhammed ;
Parkinson, Christine ;
Gale, Davina ;
Tsui, Dana W. Y. ;
Kaper, Fiona ;
Dawson, Sarah-Jane ;
Piskorz, Anna M. ;
Jimenez-Linan, Mercedes ;
Bentley, David ;
Hadfield, James ;
May, Andrew P. ;
Caldas, Carlos ;
Brenton, James D. ;
Rosenfeld, Nitzan .
SCIENCE TRANSLATIONAL MEDICINE, 2012, 4 (136)
[7]  
FUJISHIMA T, 1995, RESPIRATION, V62, P317
[8]   Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study [J].
Giaccone, Giuseppe ;
Ruiz, Marielle Gallegos ;
Le Chevalier, Thierry ;
Thatcher, Nick ;
Smit, Egbert ;
Rodriguez, Jose Antonio ;
Janne, Pasi ;
Oulid-Aissa, Dalila ;
Soria, Jean-Charles .
CLINICAL CANCER RESEARCH, 2006, 12 (20) :6049-6055
[9]   The carcinoembryonic antigen (CEA) family:: structures, suggested functions and expression in normal and malignant tissues [J].
Hammarström, S .
SEMINARS IN CANCER BIOLOGY, 1999, 9 (02) :67-81
[10]  
Han Chengbo, 2010, Zhongguo Fei Ai Za Zhi, V13, P882, DOI 10.3779/j.issn.1009-3419.2010.09.09