Serum lactate dehydrogenase activities as systems biomarkers for 48 types of human diseases.
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ABSTRACT:
SUBMITTER: Wu Y
PROVIDER: S-EPMC8217520 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThere is evidence that high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in several malignancies, but its link to cancer-specific survival is unclear.MethodsA total of 7895 individuals diagnosed with cancer between 1986 and 1999 were selected for this study. Multivariable Cox proportional hazards regression was used to assess overall and cancer-specific death by the z-score and clinical categories of serum LDH prospectively collected within 3 years before diagnosis. Site-specific analysis was performed for major cancers. Analysis was repeated by different lag times between LDH measurements and diagnosis.ResultsAt the end of follow-up, 5799 participants were deceased. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific death in the multivariable model were 1.43 (1.31-1.56) and 1.46 (1.32-1.61), respectively, for high compared with low prediagnostic LDH. Site-specific analysis showed high LDH to correlate with an increased risk of death from prostate, pulmonary, colorectal, gastro-oesophageal, gynaecological and haematological cancers. Serum LDH assessed within intervals closer to diagnosis was more strongly associated with overall and cancer-specific death.ConclusionsOur findings demonstrated an inverse association of baseline serum LDH with cancer-specific survival, corroborating its role in cancer progression.
| S-EPMC4815785 | biostudies-literature
Project description:BackgroundPatients with coronavirus disease 2019 (COVID-19) and underlying cardiovascular comorbidities have poor prognoses. Our aim was to identify the impact of serum lactate dehydrogenase (LDH), which is associated with mortality in acute respiratory distress syndrome, on the prognoses of patients with COVID-19 and underlying cardiovascular comorbidities.MethodsAmong 1518 patients hospitalized with COVID-19 enrolled in the CLAVIS-COVID (Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Diseases and/or Risk Factors study), 515 patients with cardiovascular comorbidities were analyzed. Patients were divided into tertiles based on LDH levels at admission [tertile 1 (T1), <235 U/L; tertile 2 (T2), 235-355 U/L; and tertile 3 (T3); ≥356 U/L]. We investigated the impact of LDH levels on the in-hospital mortality.ResultsThe mean age was 70.4 ± 30.0 years, and 65.3% were male. There were significantly more in-hospital deaths in T3 than in T1 and T2 [n = 50 (29.2%) vs. n = 15 (8.7%), and n = 24 (14.0%), respectively; p < 0.001]. Multivariable analysis adjusted for age, comorbidities, vital signs, and laboratory data including D-dimer and high-sensitivity troponin showed T3 was associated with an increased risk of in-hospital mortality (adjusted hazard ratio, 3.04; 95% confidence interval, 1.50-6.13; p = 0.002).ConclusionsHigh serum LDH levels at the time of admission are associated with an increased risk of in-hospital death in patients with COVID-19 and known cardiovascular disease and may aid in triage of these patients.
| S-EPMC8712257 | biostudies-literature
Project description:Phenotypic and biochemical categorization of humans with detrimental variants can provide valuable information on gene function. We illustrate this with the identification of two different homozygous variants resulting in enzymatic loss-of-function in LDHD, encoding lactate dehydrogenase D, in two unrelated patients with elevated D-lactate urinary excretion and plasma concentrations. We establish the role of LDHD by demonstrating that LDHD loss-of-function in zebrafish results in increased concentrations of D-lactate. D-lactate levels are rescued by wildtype LDHD but not by patients' variant LDHD, confirming these variants' loss-of-function effect. This work provides the first in vivo evidence that LDHD is responsible for human D-lactate metabolism. This broadens the differential diagnosis of D-lactic acidosis, an increasingly recognized complication of short bowel syndrome with unpredictable onset and severity. With the expanding incidence of intestinal resection for disease or obesity, the elucidation of this metabolic pathway may have relevance for those patients with D-lactic acidosis.
| S-EPMC6443703 | biostudies-literature
Project description:The aim of the present study was to evaluate the association between serum lactate dehydrogenase (LDH) and the risk of lymph node metastasis (LNM) in the International Federation of Gynecology and Obstetrics (FIGO) 2009 cervical cancer (CC) stages IB1-IIA2. All patient medical records with FIGO 2009 stage IB1-IIA2 CC between January 2012 and January 2022 were analyzed retrospectively. The association between serum LDH and LNM was assessed using uni- and multivariate logistic regression analyses, subgroup analyses and P-splines. The present study included 586 patients, 91 (15.5%) of whom had LNM. Patients with an elevated LDH level were more likely to have a deep stromal invasion, lymph-vascular space invasion, LNM and to be of an older age. Multivariate logistic regression revealed a significant association between LNM and LDH levels. After adjusting for age, FIGO stage, tumor markers and risk factors according to the Sedlis criteria, patients in the highest LDH quartile had an increased risk of LNM compared with those in the lowest LDH quartile (odds ratio, 3.5; 95% CI, 1.57-7.81). Furthermore, P-spline regression revealed a dependence of LNM on LDH. The predictive value of LDH level remained significant in the subgroup analysis. The present study suggested that a higher LDH level was independently associated with CC and LNM, and that LDH level may serve as a potential tumor marker and treatment-related indicator.
| S-EPMC10561153 | biostudies-literature
Project description:Lactate dehydrogenase A (LDHA) is an important enzyme in fermentative glycolysis, generating most energy for cancer cells that rely on anaerobic respiration even under normal oxygen concentrations. This renders LDHA a promising molecular target for the treatment of various cancers. Several efforts have been made recently to develop LDHA inhibitors with nanomolar inhibition and cellular activity, some of which have been studied in complex with the enzyme by X-ray crystallography. In this work, we present a molecular dynamics (MD) study of the binding interactions of selected ligands with human LDHA. Conventional MD simulations demonstrate different binding dynamics of inhibitors with similar binding affinities, whereas steered MD simulations yield discrimination of selected LDHA inhibitors with qualitative correlation between the in silico unbinding difficulty and the experimental binding strength. Further, our results have been used to clarify ambiguities in the binding modes of two well-known LDHA inhibitors.
| S-EPMC3895040 | biostudies-literature
Project description:ObjectiveThe need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinumbased chemotherapy in ovarian cancer.MethodsWe enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively.ResultsNLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters.ConclusionSerum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.
| S-EPMC7677069 | biostudies-literature
Project description:Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.
| S-EPMC8237019 | biostudies-literature
Project description:Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes.
| S-EPMC4742860 | biostudies-literature
Project description:Serum lactate dehydrogenase (LDH) has been identified as an independent risk factor for predicting all-cause mortality in patients with multiple diseases. However, the prognostic value of LDH levels in post-cardiac arrest patients remains uncertain. This study aimed to assess the association between LDH and mortality in intensive care unit (ICU) patients after cardiac arrest. This retrospective observational study is based on data from the Dryad Digital Repository, which included 374 consecutive adult patients after cardiac arrest. Patients were divided into 2 groups based on median LDH values. A multivariate Cox proportional hazards model was established to assess the independent relationship between LDH and ICU mortality. Cumulative mortality was compared using Kaplan-Meier curves. The cohort included 374 patients, of which 51.9% (194/374) died in the ICU. The overall death rate from cardiac arrest was significantly higher for patients with LDH ≥ 335 IU/L (59.6%) than for those with LDH < 335 IU/L (44.1%). In multiple Cox regression models, hazard ratios (HR) and corresponding 95% confidence intervals (CI) for logLDH and the 2 LDH groups were 1.72 (1.07, 2.78) and 1.42 (1.04, 1.93), respectively. Participants with LDH ≥ 335IU/L had a higher incidence of ICU mortality than LDH < 335 IU/L, as shown by the Kaplan-Meier curves (P = .0085). Subgroup analysis revealed that the association between LDH and ICU mortality was vitally stable, with all P interactions from different subgroups >.05. Serum LDH levels are positively associated with ICU mortality in patients after cardiac arrest, especially for patients with LDH ≥ 335 IU/L.
| S-EPMC9666175 | biostudies-literature
Project description:Preoperative serum lactate dehydrogenase (LDH) has been reported to be associated with adverse outcomes following thoracic surgery. However, its association with outcomes in noncardiac surgery as a whole has not been investigated. We conducted a retrospective cohort study at West China Hospital, Sichuan University, from 2018 to 2020, including patients undergoing noncardiac surgery. Multivariable logistic regression and propensity score weighting were employed to assess the link between LDH levels and postoperative outcomes. Preoperative LDH was incorporated into four commonly used clinical models, and its discriminative ability, reclassification, and calibration were evaluated in comparison to models without LDH. Among 130,879 patients, higher preoperative LDH levels (cut-off: 220 U/L) were linked to increased in-hospital mortality (4.382% vs. 0.702%; OR 1.856, 95% CI 1.620-2.127, P < 0.001), myocardial injury after noncardiac surgery (MINS) (3.012% vs. 0.537%; OR 1.911, 95% CI 1.643-2.223, P < 0.001), and ICU admission (15.010% vs. 6.414%; OR 1.765, 95% CI 1.642-1.896, P < 0.001). The inverse probability of treatment-weighted estimation supported these results. Additionally, LDH contributed significantly to four surgical prognostic models, enhancing their predictive capability. Our study revealed a significant association between preoperative LDH and in-hospital mortality, MINS, and ICU admission following noncardiac surgery. Moreover, LDH provided supplementary predictive information, extending the utility of commonly used surgical prognostic scores.
| S-EPMC10978990 | biostudies-literature