Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Chest Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
Int J Med Sci. 2017 Nov 2;14(13):1410-1417. doi: 10.7150/ijms.21938. eCollection 2017.
The present study evaluated the prognostic value of the epidermal growth factor receptor (EGFR) mutation status, and excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression following intercalated tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based chemotherapies (subsequent second-line treatment) for patients with adenocarcinoma non-small-cell lung cancer (AC-NSCLC). In total, 131 patients with AC-NSCLC were enrolled. The EGFR mutation status and ERCC1 and TS expression were evaluated through direct DNA sequencing and immunohistochemical analyses, respectively. The EGFR mutation status and ERCC1 and TS expression were the significant predictors of clinical outcomes. The EGFR mutation status was the main outcome predictor for overall survival (OS) benefits in the overall population. Further exploratory ERCC1 and TS expression analyses were conducted to provide additional insights. Low TS expression was predictive of improved OS of patients with negative EGFR-mutated advanced AC-NSCLC, whereas high ERCC1 expression resulted in poor OS in patients with positive EGFR-mutated advanced AC-NSCLC. TS and ERCC1 expression levels were effective prognostic factors for negative and positive EGFR-mutated AC-NSCLC, respectively. In conclusion, the present results indicate that the EGFR mutation status and TS and ERCC1 expression can be used as the predictors of OS after subsequent second-line treatments for AC-NSCLC.
本研究评估了表皮生长因子受体(EGFR)突变状态、切除修复交叉互补组 1(ERCC1)和胸苷酸合成酶(TS)表达在接受间插酪氨酸激酶抑制剂(TKI)治疗和铂类及培美曲塞化疗(二线治疗)后的腺癌非小细胞肺癌(AC-NSCLC)患者中的预后价值。共纳入 131 例 AC-NSCLC 患者。通过直接 DNA 测序和免疫组织化学分析分别评估 EGFR 突变状态、ERCC1 和 TS 表达。EGFR 突变状态和 ERCC1 和 TS 表达是临床结果的显著预测因素。EGFR 突变状态是总体人群总生存(OS)获益的主要预后预测因素。进一步进行了探索性的 ERCC1 和 TS 表达分析,以提供更多的见解。低 TS 表达预示着 EGFR 突变阴性晚期 AC-NSCLC 患者的 OS 改善,而高 ERCC1 表达则导致 EGFR 突变阳性晚期 AC-NSCLC 患者的 OS 较差。TS 和 ERCC1 表达水平是 EGFR 突变阴性和阳性 AC-NSCLC 的有效预后因素。总之,本研究结果表明,EGFR 突变状态和 TS 和 ERCC1 表达可作为 AC-NSCLC 二线治疗后 OS 的预测因素。