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 language | English |
|---|---|
| Pages (from-to) | 2560-2565 |
| Number of pages | 6 |
| Journal | Annals of Oncology |
| Volume | 24 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2013 Oct 1 |
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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 journal › Article
}
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 -