[Relationship between the expression of hypoxia-inducible factor-1alpha and chemotherapy response in gastric carcinoma].
OBJECTIVE
To evaluate the relationship of hypoxia-inducible factor (HIF)-1alpha expression with chemotherapy response in gastric cancer and its clinical outcome.


METHODS
Leucovorin (CF) and 5-fluorouracil (5-FU) in combination with oxaliplatin (L-OHP) were used in 52 patients with gastric carcinoma (GC) at advanced stage. CF 200 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. 5-FU 1500 mg/m(2) was continuously intravenous drop for 46 h at day 1 and day 14. L-OHP 85 mg/m(2) was intravenous drop for 2 h at day 1 and day 14. Four-week was one cycle. All the patients received 4 cycles of chemotherapy at least. Chemotherapy response and clinical outcome were evaluated. Immunohistochemistry was used to examine the protein expressions of HIF-1alpha, P-gp and MRP4 by tissue microarray in GC. Twenty-seven normal gastric tissue samples were used as control group.


RESULTS
The positive expression rates of HIF-lalpha, P-gp and MRP4 in tumor samples were 53.9%, 51.9% and 57.7% respectively, which were significantly higher than those in normal gastric tissues (0, 18.5% and 14.8% respectively) (P<0.05). In cases with positive expression of HIF-lalpha, the response rate was 14.3%; whereas in cases with negative expression of HIF-1alpha, the response rate was 50.0%. There was significant difference between two groups (P<0.05). In patients of HIF-1alpha positive expression,the median progression-free survival time was 4.7 months,the median survival time was 8.8 months, and 1-year, 2-year survival rates were 37.5% and 21.5% respectively. In patients of HIF-1alpha negative expression, the median progression-free survival time was 8.4 months, the median survival time was l2.6 months, and 1-year, 2-year survival rates were 51.2% and 33.5% respectively. There were significant differences between two groups (P<0.05).


CONCLUSIONS
HIF-1alpha expression may be a useful indicator to predict the chemotherapy response and clinical outcome in gastric carcinoma.
Wu
Qing
Q
Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
Li
Zhao-shen
ZS
Li
Da-wei
DW
Peng
Zhi-hai
ZH
Yang
Zhao-rui
ZR
D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D051795:Hypoxia-Inducible Factor 1, alpha Subunit