Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: Correlative study in Japan Clinical Oncology Group Trial JCOG9912

Y. Yamada, N. Boku, T. Nishina, K. Yamaguchi, T. Denda, A. Tsuji, Yasuo Hamamoto, K. Konishi, Y. Tsuji, K. Amagai, S. Ohkawa, Y. Fujita, H. Nishisaki, H. Kawai, A. Takashima, J. Mizusawa, K. Nakamura, A. Ohtsu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer. Patients and methods: Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point. Results: Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08-1.75; P = 0.010], performance status =1 (HR 1.45; 95% CI 1.13-1.86; P = 0.004), and number of metastatic sites =2 (HR 1.66; 95% CI 1.28-1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1. Conclusion: These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.

Original languageEnglish
Pages (from-to)2560-2565
Number of pages6
JournalAnnals of Oncology
Volume24
Issue number10
DOIs
Publication statusPublished - 2013 Oct 1

Fingerprint

Medical Oncology
DNA Repair
Stomach Neoplasms
Japan
Confidence Intervals
irinotecan
Genes
Dihydrouracil Dehydrogenase (NADP)
Biopsy
Gene Expression
Thymidylate Synthase
Fluorouracil
Cisplatin
Multivariate Analysis
Biomarkers
Drug Therapy
Messenger RNA
Survival
Therapeutics

Keywords

  • Dihydropyrimidine dehydrogenase
  • Excision repair cross-complementing gene 1
  • Gastric cancer
  • Prognostic factor
  • Thymidylate synthase
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer : Correlative study in Japan Clinical Oncology Group Trial JCOG9912. / Yamada, Y.; Boku, N.; Nishina, T.; Yamaguchi, K.; Denda, T.; Tsuji, A.; Hamamoto, Yasuo; Konishi, K.; Tsuji, Y.; Amagai, K.; Ohkawa, S.; Fujita, Y.; Nishisaki, H.; Kawai, H.; Takashima, A.; Mizusawa, J.; Nakamura, K.; Ohtsu, A.

In: Annals of Oncology, Vol. 24, No. 10, 01.10.2013, p. 2560-2565.

Research output: Contribution to journalArticle

Yamada, Y, Boku, N, Nishina, T, Yamaguchi, K, Denda, T, Tsuji, A, Hamamoto, Y, Konishi, K, Tsuji, Y, Amagai, K, Ohkawa, S, Fujita, Y, Nishisaki, H, Kawai, H, Takashima, A, Mizusawa, J, Nakamura, K & Ohtsu, A 2013, 'Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: Correlative study in Japan Clinical Oncology Group Trial JCOG9912', Annals of Oncology, vol. 24, no. 10, pp. 2560-2565. https://doi.org/10.1093/annonc/mdt238
Yamada, Y. ; Boku, N. ; Nishina, T. ; Yamaguchi, K. ; Denda, T. ; Tsuji, A. ; Hamamoto, Yasuo ; Konishi, K. ; Tsuji, Y. ; Amagai, K. ; Ohkawa, S. ; Fujita, Y. ; Nishisaki, H. ; Kawai, H. ; Takashima, A. ; Mizusawa, J. ; Nakamura, K. ; Ohtsu, A. / Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer : Correlative study in Japan Clinical Oncology Group Trial JCOG9912. In: Annals of Oncology. 2013 ; Vol. 24, No. 10. pp. 2560-2565.
@article{3b467e415bd64999ae6cbcb2385a2363,
title = "Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: Correlative study in Japan Clinical Oncology Group Trial JCOG9912",
abstract = "Background: Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer. Patients and methods: Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point. Results: Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95{\%} confidence interval (CI) 1.08-1.75; P = 0.010], performance status =1 (HR 1.45; 95{\%} CI 1.13-1.86; P = 0.004), and number of metastatic sites =2 (HR 1.66; 95{\%} CI 1.28-1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95{\%} CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1. Conclusion: These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.",
keywords = "Dihydropyrimidine dehydrogenase, Excision repair cross-complementing gene 1, Gastric cancer, Prognostic factor, Thymidylate synthase, Vascular endothelial growth factor",
author = "Y. Yamada and N. Boku and T. Nishina and K. Yamaguchi and T. Denda and A. Tsuji and Yasuo Hamamoto and K. Konishi and Y. Tsuji and K. Amagai and S. Ohkawa and Y. Fujita and H. Nishisaki and H. Kawai and A. Takashima and J. Mizusawa and K. Nakamura and A. Ohtsu",
year = "2013",
month = "10",
day = "1",
doi = "10.1093/annonc/mdt238",
language = "English",
volume = "24",
pages = "2560--2565",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer

T2 - Correlative study in Japan Clinical Oncology Group Trial JCOG9912

AU - Yamada, Y.

AU - Boku, N.

AU - Nishina, T.

AU - Yamaguchi, K.

AU - Denda, T.

AU - Tsuji, A.

AU - Hamamoto, Yasuo

AU - Konishi, K.

AU - Tsuji, Y.

AU - Amagai, K.

AU - Ohkawa, S.

AU - Fujita, Y.

AU - Nishisaki, H.

AU - Kawai, H.

AU - Takashima, A.

AU - Mizusawa, J.

AU - Nakamura, K.

AU - Ohtsu, A.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Background: Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer. Patients and methods: Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point. Results: Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08-1.75; P = 0.010], performance status =1 (HR 1.45; 95% CI 1.13-1.86; P = 0.004), and number of metastatic sites =2 (HR 1.66; 95% CI 1.28-1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1. Conclusion: These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.

AB - Background: Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer. Patients and methods: Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point. Results: Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08-1.75; P = 0.010], performance status =1 (HR 1.45; 95% CI 1.13-1.86; P = 0.004), and number of metastatic sites =2 (HR 1.66; 95% CI 1.28-1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1. Conclusion: These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.

KW - Dihydropyrimidine dehydrogenase

KW - Excision repair cross-complementing gene 1

KW - Gastric cancer

KW - Prognostic factor

KW - Thymidylate synthase

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=84884705232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884705232&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdt238

DO - 10.1093/annonc/mdt238

M3 - Article

C2 - 23884439

AN - SCOPUS:84884705232

VL - 24

SP - 2560

EP - 2565

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 10

ER -