Department of Hospital Pathology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea.
Int J Med Sci. 2013 Jul 31;10(9):1217-23. doi: 10.7150/ijms.6054. Print 2013.
Tumor hypoxia confers poor prognosis of a wide range of solid tumors due to increased malignancy, increased likelihood of metastasis and treatment resistance. The aim of this study was to assess the significance of the expression of HIF-1α and HIF-1α-inducible proteins in gastric cancer and their impact on prognosis.
The expression of HIF-1α, GLUT-1, CA-9, and iNOS proteins was analyzed by immunohistochemistry in 193 gastric adenocarcinomas (GAs) and 20 normal gastric mucosa.
HIF-1α, GLUT-1, CA-9 and iNOS were expressed in 52.3%, 43.0%, 57.0%, and 43.0% of GAs, respectively, which are higher than the normal counterparts except for CA-9. HIF-1α expression was positively correlated with the expression of GLUT-1, CA-9 and iNOS. GLUT-1 expression was higher in the intestinal type (p = 0.012); however, iNOS expression was higher in the less-differentiated type and the diffuse type (p = 0.006, p = 0.032, respectively). The expression of HIF-1α and GLUT-1 was significantly correlated with lymph node metastasis (p = 0.009, p = 0.008, respectively), while the expression of GLUT-1 and iNOS was significantly correlated with the depth of invasion and advanced stage (p = 0.044, p = 0.004; p = 0.009, p = 0.008, respectively). Overall survival was shorter in patients with GLUT-1 expression than in those without GLUT-1 expression, which was statistically significant by univariate analysis (p = 0.042). On multivariate analysis, however, stage was determined as the only independent prognostic marker (p < 0.001).
Our data suggest that overexpression of HIF-1α, GLUT-1, and iNOS may play an important role in gastric cancer progression. GLUT-1 is a potential candidate for predicting patient survival.
肿瘤缺氧导致广泛的实体瘤预后不良，因为它增加了恶性程度、转移的可能性和治疗抵抗性。本研究旨在评估 HIF-1α 和 HIF-1α 诱导蛋白在胃癌中的表达意义及其对预后的影响。
采用免疫组化法检测 193 例胃腺癌（GA）和 20 例正常胃黏膜中 HIF-1α、GLUT-1、CA-9 和 iNOS 蛋白的表达。
HIF-1α、GLUT-1、CA-9 和 iNOS 在 GA 中的表达率分别为 52.3%、43.0%、57.0%和 43.0%，除 CA-9 外，均高于正常对照。HIF-1α 的表达与 GLUT-1、CA-9 和 iNOS 的表达呈正相关。GLUT-1 的表达在肠型中较高（p = 0.012）；然而，iNOS 的表达在低分化型和弥漫型中较高（p = 0.006，p = 0.032）。HIF-1α 和 GLUT-1 的表达与淋巴结转移显著相关（p = 0.009，p = 0.008），而 GLUT-1 和 iNOS 的表达与浸润深度和晚期显著相关（p = 0.044，p = 0.004；p = 0.009，p = 0.008）。GLUT-1 表达阳性的患者总生存时间较阴性患者短，单因素分析有统计学意义（p = 0.042）。然而，多因素分析显示，分期是唯一独立的预后标志物（p < 0.001）。
本研究数据表明，HIF-1α、GLUT-1 和 iNOS 的过度表达可能在胃癌进展中发挥重要作用。GLUT-1 可能是预测患者生存的潜在候选标志物。
