Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis.
Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis.
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非小细胞肺癌组织中乳酸脱氢酶 5 (LDH-5) 过度表达与肿瘤缺氧、血管生成因子产生和不良预后有关。
DOI：
10.1038/sj.bjc.6601205
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发表时间：
2003-09-01
影响因子：
8.8
通讯作者：
Harris, AL
中科院分区：
文献类型：
--
作者：
Koukourakis, MI;Giatromanolaki, A;Sivridis, E;Bougioukas, G;Didilis, V;Gatter, KC;Harris, AL
乳酸脱氢酶-5（LDH-5）催化丙酮酸到乳酸的可逆转化，在厌氧细胞代谢中具有主要位置。LDH-5的诱导发生在缺氧期间，并且LDH-5转录直接受缺氧诱导因子1（HIF 1）调节。血清LDH水平与各种肿瘤疾病的预后不良和对化疗和放疗的抵抗有关。然而，LDH在肿瘤中的表达在过去从未被研究过。在本研究中，我们建立了一种免疫组织化学方法来评估肿瘤中LDH-5的过度表达，使用两种针对大鼠肌肉LDH-5和人LDH-5（Abcam，UK）的新型抗体。癌细胞中的亚细胞表达模式为细胞核和细胞质混合。与癌细胞直接相反，间质成纤维细胞仅在少数情况下对LDH-5有反应。血清LDH，虽然正相关，但不能可靠地反映肿瘤内LDH-5的状态。乳酸脱氢酶-5的过度表达与HIF 1 α和HIF 2α的表达直接相关，但与碳酸酐酶9的表达无关。LDH-5高表达的肿瘤患者预后差。LDH-5和HIF 1 α（或HIF 2 α）同时过表达的肿瘤，表明功能性HIF通路，具有特别的侵袭性行为。它的结论是，LDH-5的过度表达是一种常见的事件在非小细胞肺癌，可以很容易地评估石蜡包埋材料，并提供重要的预后信息，特别是当与其他内源性标志物的缺氧和酸度。
Lactate dehydrogenase-5 (LDH-5) catalyses the reversible transformation of pyruvate to lactate, having a principal position in the anaerobic cellular metabolism. Induction of LDH-5 occurs during hypoxia and LDH-5 transcription is directly regulated by the hypoxia-inducible factor 1 (HIF1). Serum LDH levels have been correlated with poor prognosis and resistance to chemotherapy and radiotherapy in various neoplastic diseases. The expression, however, of LDH in tumours has never been investigated in the past. In the present study, we established an immunohistochemical method to evaluate the LDH-5 overexpression in tumours, using two novel antibodies raised against the rat muscle LDH-5 and the human LDH-5 (Abcam, UK). The subcellular patterns of expression in cancer cells were mixed nuclear and cytoplasmic. In direct contrast to cancer cells, stromal fibroblasts were reactive for LDH-5 only in a minority of cases. Serum LDH, although positively correlated with, does not reliably reflect the intratumoral LDH-5 status. Lactate dehydrogenase-5 overexpression was directly related to HIF1α and 2α, but not with the carbonic anhydrase 9 expression. Patients with tumours bearing high LDH-5 expression had a poor prognosis. Tumours with simultaneous LDH-5 and HIF1α (or HIF2α) overexpression, indicative of a functional HIF pathway, had a particularly aggressive behaviour. It is concluded that overexpression of LDH-5 is a common event in non-small-cell lung cancer, can be easily assessed in paraffin-embedded material and provides important prognostic information, particularly when combined with other endogenous markers of hypoxia and acidity.
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影响因子：
11.4
作者：
Ema, M;Hirota, K;Fujii-Kuriyama, Y
通讯作者：
Fujii-Kuriyama, Y
DOI：
10.1016/s0360-3016(01)01630-3
发表时间：
2001-10-01
影响因子：
7
作者：
Brizel, DM;Schroeder, T;Mueller-Klieser, W
通讯作者：
Mueller-Klieser, W
影响因子：
13.5
作者：
BRONK, SF;GORES, GJ
通讯作者：
GORES, GJ
DOI：
10.1016/s0360-3016(02)02848-1
发表时间：
2002-08-01
影响因子：
7
作者：
Koukourakis, MI;Giatromanolaki, A;Harris, AL
通讯作者：
Harris, AL
影响因子：
9.6
作者：
Cheng, DS;Rodriguez, RM;Light, RW
通讯作者：
Light, RW