title: Excision-repair cross-complementing 1 predicts response to cisplatin-based neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.
abstract: Low excision repair cross-complementing 1 (ERCC1) has been associated with a favorable response to cisplatin (CDDP) in several types of malignancies. The present study aimed to investigate whether ERCC1 predicts the response to CDDP-based chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the association between ERCC1 and platinum drug sensitivity in ESCC cell lines. ERCC1 mRNA levels in pre- and post-treatment tumoral and normal biopsies of 16 ESCC patients receiving CDDP-based CRT and in 4 ESCC cell lines were examined using real-time reverse transcription polymerase chain reaction. Pre-treatment tumoral ERCC1 was compared with clinicopathological variables and response to CRT. Responses to CDDP and oxaliplatin (OXA) in ESCC cell lines were evaluated using the WST-8 colorimetric assay by comparing ERCC1 levels. ERCC1 was significantly higher in cancer tissue compared to normal tissue (p<0.01). Tumoral ERCC1 significantly decreased after CRT to normal levels (p<0.05). ERCC1 levels in patients with a partial response were significantly lower than levels in patients who did not respond to CRT (p<0.05). ESCC cell lines with lower ERCC1 showed significantly greater sensitivity to clinically relevant concentrations of CDDP and OXA compared to lines with higher ERCC1 (p<0.01). In conclusion, low ERCC1 levels were associated with platinum drug sensitivity in ESCC cell lines. Pre-treatment tumoral ERCC1 may be used as a predictive marker for identifying patients who respond to CRT.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, and Department of Innovative Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan. qouji@clin.medic.mie-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoe
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Koike
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Chikao
authors.initials: C
authors.lastname: Miki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tonouchi
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki