Author:
Yamada Yasuhide,Nagashima Kengo,Azuma Mizutomo,Masutani Mitsuko,Ichikawa Hitoshi,Iwasa Satoru,Takahashi Naoki,Hirano Hidekazu,Kanato Keisuke,Machida Nozomu,Kinoshita Takahiro,Hata Hiroaki,Kawakami Hisato,Takahari Daisuke,Boku Narikazu,Kurokawa Yukinori,Terashima Masanori,Yoshikawa Takaki,Sekine Shigeki,Hiraoka Nobuyoshi
Abstract
Abstract
Background
To define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers.
Methods
Endoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1.
Results
Low ERCC1 expression was associated with favorable prognosis for overall survival, OS by multivariable analysis (P = 0.001). There were significant interactions between the two treatment arms of DCS and CS, and ERCC1 mRNA expression. In patients with low ERCC1 expression of a favorable prognosis, DCS therapy was inferior to CS (P = 0.046). In addition to GSTP1 rs1695 (HR 1.728), ERCC1 rs3212980, ERCC1 rs2298881, ERCC1 rs3212964 with high expression of ERCC1 mRNA were associated with significantly worse prognosis with regard to OS.
Conclusions
ERCC1 mRNA is an independent prognostic factor and predictive marker that can be used to guide the addition of docetaxel. The SNPs of ERCC1 and GSTP1 could be also prognostic or predictive factors.
Funder
National Center for Global Health and Medicine
National Cancer Center Japan
Publisher
Springer Science and Business Media LLC