Open AccessMDM 2 is a useful prognostic biomarker for resectable gastric cancer
Author(s) -
Ye Yang,
Li Xuan,
Yang Jingjing,
Miao Shuhan,
Wang Shouyu,
Chen Yansu,
Xia Xiaowei,
Wu Xuming,
Zhang Jianbing,
Zhou Yan,
He Song,
Tan Yongfei,
Qiang Fulin,
Li Gang,
Røe Oluf Dimitri,
Zhou Jianwei
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12111
Subject(s) - medicine , cancer , oxaliplatin , oncology , biomarker , mdm2 , hazard ratio , malignancy , immunohistochemistry , gene knockdown , cancer research , colorectal cancer , confidence interval , apoptosis , biology , biochemistry
Expression of MDM 2 protein appears to be increased in malignancy and correlated to prognosis of tumors, but its role in gastric cancer remains controversial. Our recent investigations indicated that JWA was a novel candidate biomarker for gastric cancer. To evaluate the impact of MDM 2 protein expression alone, and in combination with JWA , on the prognostic and predictive of patients with resectable gastric cancer, expression of MDM 2 and JWA were examined by immunohistochemistry in three large cohorts (total n = 1131) of patient with gastric cancer. We found that MDM 2 protein levels were significantly upregulated in gastric cancer (70.4%, 57 of 81) compared with adjacent non‐cancerous tissues. High tumoral MDM 2 expression significantly correlated with clinicopathologic characteristics, as well as with shorter overall survival ( OS ; P < 0.001 for all cohorts) in patients without adjuvant treatment. The effect of adjuvant fluorouracil–leucovorin–oxaliplatin ( FLO ) in improving OS compared with surgery alone was evident only in the high MDM 2 group (hazard ratio = 0.57; 95% confidence interval, 0.37–0.89; P = 0.013). Furthermore, knockdown of MDM 2 and overexpression of JWA had a synergistic effect on suppression of gastric cancer cell proliferation and migration. Patients with low MDM 2 and high JWA expression had a better outcome of survival compared with the other groups ( P < 0.001 for all cohorts). For the first time, our data suggest that MDM 2 is a potent prognostic and predictive factor for benefit from adjuvant fluorouracil–leucovorin–oxaliplatin chemotherapy in resectable gastric cancer. The combination of MDM 2 expression and JWA could serve as a more effective candidate prognostic biomarker for gastric cancer.