Aberrant methylation of p16 predicts candidates for 5-fluorouracil-based adjuvant therapy in gastric cancer patients.
BACKGROUND
Aberrant methylation of some cancer-related genes has been reported to correlate with sensitivity to chemotherapeutic agents. The present study was designed to determine whether DNA methylation in six cancer-related genes affects recurrence of gastric cancer in patients who received 5-fluorouracil-based adjuvant chemotherapy.


METHODS
The methylation status of six genes, MGMT, CHFR, hMLH1, p16INK4a, E-cadherin, and Runx3, was analyzed in 56 surgically resected gastric cancer tissue specimens by methylation-specific polymerase chain reaction. Of the 56 patients who underwent surgical resection, 38 received 5-fluorouracil (5-FU)-based adjuvant chemotherapy postoperatively (adjuvant group), whereas the other 18 (32%) did not (surgery group).


RESULTS
There were no significant differences between the two groups with respect to sex, cancer differentiation, depth of tumor invasion, lymph node metastasis, lymphatic invasion, vascular invasion and tumor stage. Among the genes, methylation of p16INK4a showed a significant correlation with longer survival in the 38 patients of the adjuvant group, but not in the 18 patients of the surgery group. A multivariate analysis identified p16INK4a methylation to be an independent factor predicting a longer recurrence-free period under 5-FU-based adjuvant chemotherapy.


CONCLUSIONS
The present study demonstrated for the first time that gastric cancer patients with p16INK4a methylation specifically benefit from 5-FU-based adjuvant chemotherapy.
Mitsuno
Mayumi
M
Department of Surgery, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Kitajima
Yoshihiko
Y
Ide
Takao
T
Ohtaka
Kazuma
K
Tanaka
Masayuki
M
Satoh
Seiji
S
Miyazaki
Kohji
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D018279:Carcinoma, Signet Ring Cell / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000706:statistics & numerical data; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D005472:Fluorouracil