LDH5 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis

Abstract

Lactate dehydrogenase 5 (LDH5) is believed to be particularly important and a reliable marker of malignancy. However, it is still controversial whether LDH5 expression can be regarded as a prognostic factor for cancer patients. We reviewed the literature by performing an electronic database search via PubMed to identify eligible studies that assessed the impact of LDH5 as a cancer prognostic marker and its association with HIF-1α. Heterogeneity and publication bias were also assessed. A total of 12 literatures which included 1,892 cancer patients were combined in the final analysis. Meta-analysis revealed that LDH5 overexpression was associated with an unfavorable overall survival (12 studies, 1,597 patients; HR 1.59, 95 % CI 1.17-2.16) and disease/recurrence/progression-free survival (7 studies; 1,086 patients; HR 1.46, 95 % CI 1.04-2.04) among solid tumor patients. Meta-analysis revealed an association between the expression of LDH5 and hypoxia-inducible factors 1 (OR 2.72, 95 % CI 1.66-4.45). Publication bias could not be excluded when investigating the association of LDH5 expression and overall survival. However, when we accounted for publication bias using the trim and fill method, the results remained significant (HR 1.435, 95 % CI 1.071-1.923, P < 0.05) suggesting the stability of our results. Therefore, our study suggested that LDH5 overexpression had a poor prognosis value in cancer patients. The results of this meta-analysis suggest that high LDH5 expression is associated with HIF-1α and poor overall survival in cancer patients.

Prognostic value of preoperative serum lactate dehydrogenase in thymic carcinoma

“…In addition, both Masaoka stage and complete resection were independent prognostic indicators of OS and PFS in these thymic carcinoma patients, which is consistent with previous reports (20,21). Patients with IIIa & IIIb 29 [41] 11 [46] IVa & IVb 11 [15] 11 [46] LDH, lactate dehydrogenase; SD, standard deviation. thymic carcinoma and complete resection are known to have better survival than those with incomplete resection (20).…”

“…Increase in the number of LDH-A subunits (LDH-5) in a tetramer favors the conversion of pyruvate to lactate; increase of LDH-B subunits (LDH-1) favors the conversion of pyruvate to acetyl-CoA that enters the TCA cycle (39,40). A recent meta-analysis of 12 studies concluded that LDH-5 overexpression is associated with poor survival in patients with solid tumors, including head and neck squamous cell cancer, colorectal adenocarcinoma, renal clear cell carcinoma, oral squamous cell carcinoma, non-small cell lung cancer (NSCLC), melanoma, gastric cancer, and endometrial cancer (41).…”

Current relevance of hypoxia in head and neck cancer

“…Oropharyngeal tumors have higher LDH5 expression than other head and neck tumors. The serum LDH level in HNSCC patients is an independent prognostic factor and Hsieh et al [116] and Yao et al [117] found that serum LDH above the upper limit of normal correlates with poor survival. LDH activity in saliva has also been correlated with periodontal disease [118].…”

Monitoring a ‘metabolic shift’ after surgical resection of oral squamous cell carcinomas by serum lactate dehydrogenase

“…Measured by immunohistochemistry, our previous study demonstrated LDH‐5 expression, which is the most efficient isoenzyme catalyzing the conversion of pyruvate to lactate as an independent prognostic factor for reduced tumor‐specific survival in OSCC . Therefore, focusing on the LDH‐5 isoform (M subunit) is of potential therapeutic interest by targeted therapies ( e.g., small compounds) for oncologists .…”

“…reduced tumor-specific survival in OSCC (35). Therefore, focusing on the LDH-5 isoform (M subunit) is of potential therapeutic interest by targeted therapies (e.g., small compounds) for oncologists (36,47,48).…”