Comparative efficacy of serum lactate dehydrogenase levels versus circulating cell-free microRNAs in monitoring response to checkpoint inhibitor immunotherapy treatment in metastatic melanoma patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157370 | GEO | 2020/12/07
REPOSITORIES: GEO
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Project description:Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients' and 73 normal donors' plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors' plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII.
| S-EPMC7696545 | biostudies-literature
Project description:Comparative efficacy of serum lactate dehydrogenase levels versus circulating cell-free microRNAs in monitoring response to checkpoint inhibitor immunotherapy treatment in metastatic melanoma patients
| PRJNA661067 | ENA
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:Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Despite the high prevalence of C. parvum, there are no fully effective and safe drugs for treating infections, and there is no vaccine. We have previously reported that the bacterial-like C. parvum lactate dehydrogenase (CpLDH) enzyme is essential for survival, virulence and growth of C. parvum in vitro and in vivo. In the present study, we screened compound libraries and identified inhibitors against the enzymatic activity of recombinant CpLDH protein in vitro. We tested the inhibitors for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers and identified compounds NSC158011 and NSC10447 that inhibited the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, we found that both NSC158011 and NSC10447 consistently significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces, and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. Together, our findings have unveiled promising anti-Cryptosporidium drug candidates that can be explored further for the development of the much needed novel therapeutic agents against C. parvum infections.
| S-EPMC6687188 | 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: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:Most human diseases are systems diseases, and systems biomarkers are better fitted for diagnostic, prognostic, and treatment monitoring purposes. To search for systems biomarker candidates, lactate dehydrogenase (LDH), a housekeeping protein expressed in all living cells, was investigated. To this end, we analyzed the serum LDH activities from 172,933 patients with 48 clinically defined diseases and 9528 healthy individuals. Based on the median values, we found that 46 out of 48 diseases, leading by acute myocardial infarction, had significantly increased (p < 0.001), whereas gout and cerebral ischemia had significantly decreased (p < 0.001) serum LDH activities compared to the healthy control. Remarkably, hepatic encephalopathy and lung fibrosis had the highest AUCs (0.89, 0.80), sensitivities (0.73, 0.56), and specificities (0.90, 0.91) among 48 human diseases. Statistical analysis revealed that over-downregulation of serum LDH activities was associated with blood-related cancers and diseases. LDH activities were potential systems biomarker candidates (AUCs > 0.8) for hepatic encephalopathy and lung fibrosis.
| S-EPMC8217520 | 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:BackgroundRecently, many studies have shown that the serum lactate dehydrogenase (LDH) level is related to the prognosis of renal cell carcinoma (RCC). We launched this meta-analysis to assess the prognostic value of serum LDH in patients with RCC.MethodsWe searched PubMed, Embase and Web of Science for information on serum LDH and the outcome of RCC through June 14, 2016. The hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) were extracted and integrated from the matching studies.ResultsA total of 29 studies including 6629 patients with RCC were incorporated in this meta-analysis. Patients whose serum LDH levels were elevated had a lower OS (HR = 2.13, 95% CI = 1.69-2.69, P < 0.001). Meanwhile, the pooled data showed that a higher serum LDH level was a negative prognostic factor for PFS (HR = 1.74, 95% CI = 1.48-2.04, P < 0.001). Furthermore, subgroup analyses indicated elevated serum LDH was associated with poor survival in different tumor types. Elevated serum LDH was significantly associated with worse prognosis for patients with all stages of RCC (OS, HR = 2.41, 95% CI = 1.09-5.33), metastatic RCC (OS, HR = 2.62, 95% CI 1.57-2.59; CSS, HR = 1.79, 95% CI 1.49-2.15), and non-metastatic RCC (OS, HR = 3.67, CI = 1.33-10.13). Besides, elevated serum LDH also indicated a worse prognosis in subgroups of cut-off values, analysis types and ethnicity.ConclusionsOur results show that serum LDH levels are associated with the outcomes of RCC and can be used as a valuable biomarker for monitoring prognoses.
| S-EPMC5115746 | biostudies-literature
Project description:BackgroundEstablished prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis.MethodsWe analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan-Meier survival probabilities and multivariate Cox hazard regression analysis.ResultsSerum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%).ConclusionThe serum markers LDH and S100B were both found to be prognostic factors in melanoma patients with distant metastasis. Furthermore, complete metastasectomy had an independent favourable prognostic impact in particular for the patient subgroup with normal LDH and S100B values.
| S-EPMC3405231 | biostudies-literature