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血清癌胚抗原(CEA)水平升高与携带表皮生长因子受体(EGFR)突变的肺腺癌的快速进展相关。

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

作者信息

Gao Yuan, Song PingPing, Li Hui, Jia Hui, Zhang BaiJiang

机构信息

Department of Thoracic Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, 250117, China.

Department of Thoracic Surgery, Shandong Tumor Hospital and Institute, Jinan, Shandong Province, 250117, China.

出版信息

BMC Cancer. 2017 Jul 14;17(1):484. doi: 10.1186/s12885-017-3474-3.

Abstract

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 ~ 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.

摘要

背景

血清癌胚抗原(CEA)水平是表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)疗效的预测指标,且与表皮生长因子受体(EGFR)基因突变相关。然而,对于具有敏感EGFR突变的肺腺癌患者,在不同靶向治疗周期中血浆CEA水平变化的临床意义尚不清楚。

方法

2011年至2015年期间,共有155例肺腺癌患者纳入本回顾性研究。通过逆转录聚合酶链反应(RT-PCR,实时定量聚合酶链反应)检测EGFR突变。在不同EGFR-TKI治疗周期前测量血浆CEA水平。每2个月进行一次计算机断层扫描(CT)以评估治疗效果。

结果

血清CEA浓度与EGFR突变显著相关(p<0.05)。此外,在所有接受EGFR-TKIs治疗的患者中,血清CEA水平随疾病进展而升高(p<0.005)。COX多因素分析显示,CEA水平高于正常16.2倍与疾病早期进展相关(风险比[HR],5.77;95%置信区间[CI]:2.36~14.11;p<0.001)。基于这一发现,将阈值设定在中位时间8.3个月。具有EGFR突变的患者中位无进展生存时间为12.8个月。对于对EGFR-TKIs耐药的患者,与通过CT扫描检测到变化前4.5个月测量的水平相比,血清CEA水平显著升高。

结论

与传统成像方法相比,靶向治疗期间CEA水平升高可能是携带突变EGFR的肺腺癌患者爆发性进展更敏感预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7953/5512835/83a10f37e35e/12885_2017_3474_Fig1_HTML.jpg

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