MDM2 is a useful prognostic biomarker for resectable gastric cancer.
Expression of MDM2 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 MDM2 protein expression alone, and in combination with JWA, on the prognostic and predictive of patients with resectable gastric cancer, expression of MDM2 and JWA were examined by immunohistochemistry in three large cohorts (total n = 1131) of patient with gastric cancer. We found that MDM2 protein levels were significantly upregulated in gastric cancer (70.4%, 57 of 81) compared with adjacent non-cancerous tissues. High tumoral MDM2 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 MDM2 group (hazard ratio = 0.57; 95% confidence interval, 0.37-0.89; P = 0.013). Furthermore, knockdown of MDM2 and overexpression of JWA had a synergistic effect on suppression of gastric cancer cell proliferation and migration. Patients with low MDM2 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 MDM2 is a potent prognostic and predictive factor for benefit from adjuvant fluorouracil-leucovorin-oxaliplatin chemotherapy in resectable gastric cancer. The combination of MDM2 expression and JWA could serve as a more effective candidate prognostic biomarker for gastric cancer.
Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
Yang
Y
Ye
Xuan
X
Li
Jingjing
J
Yang
Shuhan
S
Miao
Shouyu
S
Wang
Yansu
Y
Chen
Xiaowei
X
Xia
Xuming
X
Wu
Jianbing
J
Zhang
Yan
Y
Zhou
Song
S
He
Yongfei
Y
Tan
Fulin
F
Qiang
Gang
G
Li
Oluf Dimitri
OD
Røe
Jianwei
J
Zhou
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D002955:Leucovorin / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
C484566:ARL6IP5 protein, human; D014408:Biomarkers, Tumor; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002955:Leucovorin; D005472:Fluorouracil