高乳酸脱氢酶 5 表达与胃癌中肿瘤和基质血管内皮生长因子表达相关。

High lactate dehydrogenase 5 expression correlates with high tumoral and stromal vascular endothelial growth factor expression in gastric cancer.

机构信息

Department of Pathology, Chung Ang University, Seoul, Republic of Korea.

出版信息

Pathobiology. 2014;81(2):78-85. doi: 10.1159/000357017. Epub 2013 Dec 31.

DOI:10.1159/000357017

PMID:24401755

Abstract

BACKGROUND

Lactate dehydrogenase 5 (LDH5) is a major lactate dehydrogenase isoenzyme catalyzing the transformation of pyruvate to lactate to provide anaerobic energy. Vascular endothelial growth factor (VEGF) is expressed in both tumor and stromal cells in gastric cancer. Our aim was to study the prognostic effect of LDH5, and tumoral and stromal expression of the angiogenic factor VEGF in gastric cancer, and the intercorrelation of tissue expression of both factors.

METHODS

Tissue microarray analysis of 382 consecutive gastric cancer resection specimens was used for immunohistochemistry of LDH5 and VEGF, and expression of LDH5, tumoral VEGF, and stromal VEGF was categorized into low and high groups.

RESULTS

High expression was observed for LDH5 in 57.9% (219/378), tumoral VEGF in 35.7% (136/381), and stromal VEGF in 58.5% (223/381) of the specimens. Regarding high expression of LDH5 and VEGF, significant associations with intestinal type, advanced gastric cancer, lymph node metastasis, higher TNM stage, and upper-third location were noted. Positive intercorrelations occurred among the expression of LDH5 and VEGF. Results of survival analyses revealed a significant association of high expression of LDH5 and VEGF with lower survival (overall and disease-free survival). Five-year survival rates were significantly lower in tumors with high LDH5 and tumoral VEGF expression in diffuse- or mixed-type cancers and high expression of stromal VEGF in intestinal-type cancer.

CONCLUSION

The results of our study showed that high LDH5 and VEGF expression in both tumor and stroma was a prognostic factor for patients with gastric cancers, especially diffuse- or mixed-type cancers. Therefore, LDH5 expression may play a role in the regulation of tumoral and stromal VEGF expression in gastric cancer. Our results suggest the potential use of LDH5 expression as a biomarker for response to VEGF-targeted therapy.

摘要

背景

乳酸脱氢酶 5（LDH5）是一种主要的乳酸脱氢酶同工酶，可催化丙酮酸向乳酸的转化，为无氧能量提供支持。血管内皮生长因子（VEGF）在胃癌的肿瘤细胞和基质细胞中均有表达。我们的目的是研究 LDH5 以及血管生成因子 VEGF 在胃癌中的预后作用，以及这两种因子的组织表达之间的相关性。

方法

使用组织微阵列分析了 382 例连续胃癌切除标本的免疫组织化学，用于 LDH5 和 VEGF 的免疫组化，将 LDH5、肿瘤 VEGF 和基质 VEGF 的表达分为低表达和高表达两组。

结果

在 378 例标本中的 57.9%（219/378）观察到 LDH5 高表达，在 381 例标本中的 35.7%（136/381）观察到肿瘤 VEGF 高表达，在 381 例标本中的 58.5%（223/381）观察到基质 VEGF 高表达。关于 LDH5 和 VEGF 的高表达，与肠型、晚期胃癌、淋巴结转移、较高的 TNM 分期和上三分之一的位置有显著相关性。LDH5 和 VEGF 的表达之间存在阳性相关性。生存分析的结果表明，LDH5 和 VEGF 的高表达与生存率降低（总生存率和无病生存率）显著相关。在弥漫型或混合型癌症中，肿瘤中高 LDH5 和肿瘤 VEGF 表达以及在肠型癌症中基质 VEGF 高表达的肿瘤，其 5 年生存率显著降低。