title: Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies.
abstract: BACKGROUND
  In cancer cells, metabolism is shifted to aerobic glycolysis with lactate production coupled with a higher uptake of glucose as the main energy source. Lactate dehydrogenase (LDH) catalyzes the reduction of pyruvate to form lactate, and serum level is often raised in aggressive cancer and hematological malignancies. We have assessed the prognostic value of LDH in solid tumors.
  
  
  METHODS
  A systematic review of electronic databases was conducted to identify publications exploring the association of LDH with clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) were pooled in a meta-analysis. Pooled HRs were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided.
  
  
  RESULTS
  Seventy-six studies comprising 22 882 patients, mainly with advanced disease, were included in the analysis. Median cut-off of serum LDH was 245 U/L. Overall, higher LDH levels were associated with a HR for OS of 1.7 (95% CI 1.62-1.79; p < 0.00001) in 73 studies. The prognostic effect was highest in renal cell, melanoma, gastric, prostate, nasopharyngeal and lung cancers (all p < 0.00001). HRs for PFS was 1.75 (all p < 0.0001).
  
  
  CONCLUSIONS
  A high serum LDH level is associated with a poor survival in solid tumors, in particular melanoma, prostate and renal cell carcinomas, and can be used as a useful and inexpensive prognostic biomarker in metastatic carcinomas.
authors.affiliation: Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio , Treviglio (BG) , Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.forename: Mary
authors.initials: M
authors.lastname: Cabiddu
authors.forename: Andrea
authors.initials: A
authors.lastname: Coinu
authors.forename: Karen
authors.initials: K
authors.lastname: Borgonovo
authors.forename: Mara
authors.initials: M
authors.lastname: Ghilardi
authors.forename: Veronica
authors.initials: V
authors.lastname: Lonati
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
mesh_terms: D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D009369:Neoplasms / Q000097:blood* / Q000201:enzymology / Q000401:mortality; D011379:Prognosis
chemical_list: D007770:L-Lactate Dehydrogenase