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Int J Med Sci. 2017 Nov 2;14(13):1410-1417. doi: 10.7150/ijms.21938. eCollection 2017.

Evaluating the Prognostic Value of ERCC1 and Thymidylate Synthase Expression and the Epidermal Growth Factor Receptor Mutation Status in Adenocarcinoma Non-Small-Cell Lung Cancer.

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Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Chest Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
Department of Chest Medicine, Cheng-Ching General Hospital, Taichung, Taiwan.
Research Assistant Center, ChangHua Show Chwan Health Care System, Changhua, Taiwan.
Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
Division of Chest, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.


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.


EGFR mutation status; ERCC1 expression; TS protein expression; chemotherapy.; non-small-cell lung cancer; tyrosine-kinase inhibitor

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