2023Research SquareOpen access

Predictive and prognostic value of excision repair cross-complementing group 1 by multi-omics on the outcomes in patients with advanced gastric cancer

Yasuhide Yamada, Kengo Nagashima, Mizutomo Azuma, Mitsuko Masutani, Hitoshi Ichikawa, Satoru Iwasa, Naoki Takahashi, Hidekazu Hirano, Keisuke Kanato, Nozomu Machida, Takahiro Kinoshita, Hiroaki Hata, Hisato Kawakami, Daisuke Takahari, Narikazu Boku, Yukinori Kurokawa, Masanori Terashima, Takaki Yoshikawa, Shigeki Sekine, Nobuyoshi Hiraoka

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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. Clinical Trial Number: UMIN000007652

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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. Clinical Trial Number: UMIN000007652

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Available 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. Clinical Trial Number: UMIN000007652

Key concepts: ERCC1, Medicine, GSTP1, Docetaxel, Internal medicine, Predictive marker, Oncology, Cisplatin

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Predictive and prognostic value of excision repair cross-complementing group 1 by multi-omics on the outcomes in patients with advanced gastric cancer — Research Paper | ScholarLens