HIF-1α is an unfavorable determinant of relapse in gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy
✍ Scribed by Jun Nakamura; Yoshihiko Kitajima; Keita Kai; Kazuyoshi Hashiguchi; Masatsugu Hiraki; Hirokazu Noshiro; Kohji Miyazaki
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- French
- Weight
- 707 KB
- Volume
- 127
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Among several chemotherapeutic agents, 5‐fluorouracil (5‐FU) has been widely used as a key drug in adjuvant chemotherapy for gastric cancer. However, no reliable marker, which predicts the response to 5‐FU in an adjuvant setting, has been identified. Hypoxia‐induced drug resistance, via upregulation of HIF‐1α, is a major obstacle in the development of effective cancer therapy. However, few clinical studies have so far assessed the relationship between the HIF‐1α expression and the chemo‐resistance of gastric cancer patients in an adjuvant setting. We established 2 HIF‐1α knockdown gastric cancer cell lines in order to clarify the role of HIF‐1α in chemo‐resistance against 5‐FU. Furthermore, expression of HIF‐1α was immunohistochemically assessed in 91 resected specimens. Sixty‐four of 91 patients received 5‐FU adjuvant chemotherapy after surgery. HIF‐1α expression was associated with the significantly shorter relapse‐free survival and disease‐specific survival in the 64 patients of adjuvant group (p = 0.026, 0.014, respectively), but not in the 27 of surgery group. Multivariate analysis showed that HIF‐1α was an independent risk factor for relapse in 64 patients in the adjuvant group (p = 0.029). In conclusion, the current study confirmed, for the first time that HIF‐1α expression is an independent risk factor for relapse in high‐risk gastric cancer patients who underwent curative surgery followed by adjuvant 5‐FU chemotherapy. A favorable effect of 5‐FU might therefore be expected in patients that do not express HIF‐1α, whereas, other types of chemotherapy or additional treatments, such as HIF‐1α inhibitors, should be considered in patients that do express HIF‐1α.