Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer:: Association with hypoxia-inducible factor (HIF-1α) pathway, angiogenic factors production and poor prognosis
Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer:: Association with hypoxia-inducible factor (HIF-1α) pathway, angiogenic factors production and poor prognosis
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DOI：
10.1245/s10434-008-9955-5
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发表时间：
2008-08-01
影响因子：
3.7
通讯作者：
Sugihara, Kenichi
中科院分区：
文献类型：
--
作者：
Kolev, Yanislav;Uetake, Hiroyuki;Sugihara, Kenichi
背景资料：乳酸脱氢酶-5（LDH-5）是一种在低氧条件下将丙酮酸转化为乳酸的重要同工酶，可能在恶性肿瘤的发生和发展中起重要作用。然而，LDH-5在胃癌中的作用仍不清楚。方法：采用免疫组化法检测152例不同病理分级、不同分期胃癌组织中LDH-5的表达，并分析其临床意义。此外，缺氧诱导因子1 α（HIF-1 α）作为肿瘤缺氧的标志物，以及血管内皮生长因子（VEGF）和环氧合酶-2（考克斯-2）作为血管生成参数也在本研究中进行了评估。结果：LDH-5高表达94例（61.8%），HIF-1 α高表达95例（62.5%）。LDH-5表达与HIF-1 α、VEGF、考克斯-2呈正相关。LDH-5的过度表达在具有阳性血管浸润的晚期肿瘤中更普遍。与LDH-5低表达患者相比，LDH-5过表达患者的无病生存率（63.5% vs 82.7%）和总生存率（56.3% vs 78.4%）要低得多。HIF-1 α表达对生存率无显著影响。结论：LDH-5高表达可能是胃癌患者的一个有用的预后指标。
Background: Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma.Methods: LDH-5 expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1 alpha (HIF-1 alpha) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.Results: There were 94 cases (61.8%) showing high LDH-5 expression, and 95 patients (62.5%) had high HIF-1 alpha expression. Positive correlation was found between LDH-5 expression and HIF-1 alpha, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1 alpha expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.Conclusion: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.