3939

LDHA

lactate dehydrogenase A;LDHA;lactate dehydrogenase A

L-lactate dehydrogenase A chain|LDH muscle subunit|LDH-A|LDH-M|cell proliferation-inducing gene 19 protein|epididymis secretory sperm binding protein Li 133P|lactate dehydrogenase M|proliferation-inducing gene 19|renal carcinoma antigen NY-REN-59

11p15.4

protein-coding

OBJECTIVES: We assessed the expression and the prognostic role of lactate dehydrogenase 5 (LDH5, the major LDH isoenzyme involved in anaerobic glycolysis) in patients with squamous cell head and neck cancer (SCHNC). METHODS: LDH5 was assessed immunohistochemically in whole tissue sections from 141 patients with SCHNC. Of these, 102 were subjected to surgery with (90 patients) or without (12 patients) postoperative radiotherapy (group A), while 39 patients were treated with radical radiotherapy (group B). RESULTS: Mixed nuclear/cytoplasmic LDH5 expression was detected in 72.5% of group A and 61.5% of group B patients. This was significantly related to T4-stage (p = 0.04) and hypoxia-inducible factor-1alpha (HIF-1alpha) expression (p = 0.002). In group A, high LDH5 was linked with poorer distant metastasis-free survival (p = 0.01) and disease-specific overall survival (OS; p = 0.009). In multivariate analysis, LDH5 (p = 0.002) and HIF-1alpha (p = 0.01) were independently linked with distant metastasis. LDH5 was also linked with death events (p = 0.005). In group B, high LDH5 expression was significantly associated with poorer local relapse-free survival (p = 0.009) and OS (p = 0.01). In multivariate analysis, only T stage was a significant predictor of death events (p = 0.04). CONCLUSIONS: LDH5 is highly expressed in SCHNC and is linked with local relapse, survival and distant metastasis, suggesting that LDH5 is a marker of radioresistance and a target for therapeutic interventions.

In previous studies, lactate dehydrogenase A (LDHA) was identified as one of the leading genes that promote the proliferative and tumorigenic potential of malignancies. However, less definitive evidence was reported in hepatocellular carcinoma (HCC) cells. Furthermore, the role of LDHA in promoting metastasis of HCC, and its possible mechanism, is not clear. In this study, RNA interference (RNAi) mediated by lentiviral vectors (which induce strong down-regulation of gene expression) was used to analyze the role of LDHA in tumor growth and metastasis in HCC. We performed transient and stable RNAi knockdowns of LDHA in HCCLM3 cells, a line that over-expresses LDHA and has a high metastatic potential. Our studies reveal that previously unidentified effects of LHDA may mediate tumor growth and metastasic effects in HCC. First, HCC cell lines over-express LDHA. Second, LDHA inhibition results in increased apoptosis via production of reactive oxygen species in HCCLM3 cells. Thus, LDHA knockdown resulted in significant reduction in metastatic potential in a xenograft mouse model. Furthermore, we found that FAK, MMP-2, VEGF and E-cadherin proteins contribute to inhibitory effects on metastasis in HCC cells. These studies have important implications for understanding the mechanisms by which LDHA promotes tumor growth and metastasis.

Accurate prognostic information is desirable when counselling patients with brain metastases regarding their therapeutic options and life expectancy. Based on previous studies, we selected serum lactate dehydrogenase (LDH) as a promising factor on which we perform a pilot study investigating methodological aspects of biomarker studies in patients with brain metastases, before embarking on large-scale studies that will look at a larger number of candidate markers in an expanded patient cohort. For this retrospective analysis, 100 patients with available information on LDH treated with palliative whole-brain radiotherapy were selected. A comprehensive evaluation of different LDH-based variables was performed in uni- and multivariate tests. Probably, the most intriguing finding was that LDH kinetics might be more important, or at least complement, information obtained from a single measurement immediately before radiotherapy. LDH and performance status outperformed several other variables that are part of prognostic models such as recursive partitioning analyses classes and graded prognostic assessment score. LDH kinetics might reflect disease behaviour in extracranial metastatic and primary sites without need for comprehensive imaging studies and is a quite inexpensive diagnostic test. Based on these encouraging results, confirmatory studies in a larger cohort of patients are warranted.

BACKGROUND AND OBJECTIVE: The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. This study aimed to evaluate whether serum lactic dehydrogenase (S-LDH) level had a clinical value in predicting clinical response and survival outcome for patients with metastatic NPC. METHODS: S-LDH level was measured at baseline and then before every cycle of treatment in 689 NPC patients with distant metastases. Correlations of pre-treatment and post-treatment S-LDH levels to response of treatment and survival were analysed retrospectively. RESULTS: Patients with elevated values of pre-treatment S-LDH (>245 IU/L) had significantly worse survival than those with normal values of pre-treatment S-LDH (

Oral squamous cell carcinoma (OSCC) account for more than 90 % of all oral malignant lesions. Lactate dehydrogenase 5 (LDH5) has the highest efficiency among all other isoenzymes to catalyse pyruvate transformation to lactate and is significantly overexpressed in several different tumour entities. LDH5 overexpression confers an advantage on malignant cells, allows them to grow faster, and to metastasize. No data regarding LDH5 expression and OSCC outcome are available. expression of LDH5 was analysed in OSCC specimen (n = 191) and cancer cell lines (BICR3, BICR56) by immunohistochemistry, real-time quantitative reverse transcription-PCR (RT-PCR) analysis, and western blotting. Scanned images were digitally analysed using ImageJ and the immunomembrane plug-in. LDH5 expression on protein level was correlated with clinicopathological characteristics and impact on survival. LDH5 was co-labelled with glucose transporter-1 (GLUT-1), Ki-67, and hypoxia inducible factor 1 (HIF-1alpha) in immunohistochemical double staining experiments. expression subgroups were identified by receiver operating characteristics analysis. LDH5 expression was significantly associated with tumour progression, and recurrence of the tumour. Multivariate analysis demonstrated LDH5 expression as an independent prognostic factor (p < 0.0001). Immunohistochemical double staining experiments revealed LDH5 expression by cancer cells in association with glucose uptake (GLUT-1), proliferation (Ki-67), and hypoxia (HIF-1alpha). LDH5 specificity was confirmed by western blot and RT-PCR analysis. For the first time, this study provides evidence that LDH5 expression in OSCC might be associated with tumour formation and metastasis in a large patient cohort. Therefore, adjuvant therapies targeting glucose metabolism might be promising for therapy of OSCC.