Serum lactate dehydrogenase and survival following cancer diagnosis

Wulaningsih, Wahyu; Holmberg, Lars; Garmo, Hans; Malmström, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Ng, Tony; Hemelrijck, Mieke Van

doi:10.1038/bjc.2015.361

Cited by 80 publications

(68 citation statements)

References 48 publications

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“…LDHA and B are responsible for encoding the M and H subunits of LDH and the high Ldha / Ldhb expression ratio observed in high-grade TRAMP tumors leads to the production of a predominance of the LDH5 isoenzyme (5M subunits) favoring increased lactate production. In patient studies, a high serum LDH level is associated with aggressive disease and a poor survival for a variety of cancers (24,25) including prostate cancer (26), and inhibition of the LDH catalyzed production of lactate has become a therapeutic target (27,28). Studies using patient biopsies and prostate tissue slices removed at surgery have demonstrated increased steady state pools of lactate, HP 13 C-lactate production, increased LDH activity, and increased mRNA expression of LDHA and MCT1 and 4 in prostate cancer tissues similar to what has been observed in the TRAMP model used in this study (29).…”

Section: Discussionmentioning

confidence: 99%

Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion

et al. 2017

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New magnetic resonance (MR) molecular imaging techniques offer the potential for non-invasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a 3D dynamic dual-agent hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) approach with 13C-pyruvate and 13C-urea to investigate differences in perfusion and metabolism between low and high grade tumors in the TRAMP transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade. kPL values were relatively higher for high-grade TRAMP tumors. The increase in kPL flux correlated significantly with higher lactate dehydrogenase activity and mRNA expression of Ldha, Mct1 and Mct4 as well as with more proliferative disease. There was a significant reduction in perfusion in high-grade tumors that associated with increased hypoxia and mRNA expression of Hif1α and Vegf and increased ktrans, attributed to increased blood vessel permeability. In 90% of the high-grade TRAMP tumors, a mismatch in perfusion and metabolism measurements was observed, with low perfusion being associated with increased kPL. This perfusion-metabolism mismatch was also associated with metastasis. The molecular imaging approach we developed could be translated to investigate these imaging biomarkers for their diagnostic and prognostic power in future prostate cancer clinical trials.

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Section: Discussionmentioning

confidence: 99%

Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion

et al. 2017

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“…Koehler et al65 detected an association between abnormal GGT values and mortality in older people. Wulaningsih et al66 and Liu et al67 found that increased serum LDH values predicted mortality.…”

Section: Discussionmentioning

confidence: 99%

Operationalizing a frailty index using routine blood and urine tests

Ritt

Jäger²,

Ritt³

et al. 2017

CIA

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BackgroundUncomplicated frailty instruments are desirable for use in a busy clinical setting. The aim of this study was to operationalize a frailty index (FI) from routine blood and urine tests, and to evaluate the properties of this FI compared to other frailty instruments.Materials and methodsWe conducted a secondary analysis of a prospective cohort study on 306 patients aged ≥65 years hospitalized on geriatric wards. An FI comprising 22 routine blood parameters and one standard urine parameter (FI-Lab), a 50-item FI based on a comprehensive geriatric assessment (FI-CGA), a combined FI (FI-combined [items from the FI-Lab + others from the FI-CGA]), the Clinical Frailty Scale, rule-based frailty definition, and frailty phenotype were operationalized from data obtained during patients’ hospital stays (ie, before discharge [baseline examination]). Follow-up data were obtained up to 1 year after the baseline examination.ResultsThe mean FI-Lab score was 0.34±15, with an upper limit of 0.74. The FI-Lab was correlated with all the other frailty instruments (all P<0.001). The FI-Lab revealed an area under the receiver-operating characteristic curve (AUC) for 6-month and 1-year mortality of 0.765 (0.694–0.836) and 0.769 (0.706–0.833), respectively (all P<0.001). Each 0.01 increment in FI-Lab increased the risk (adjusted for age and sex) for 6-month and 1-year mortality by 7.2% and 7.1%, respectively (all adjusted P<0.001). When any of the other FIs (except the FI-combined) were also included in the models, each 0.01 increment in FI-Lab score was associated with an increase in the risk of 6-month and 1-year mortality by 4.1%–5.4% (all adjusted P<0.001).ConclusionThe FI-Lab showed key characteristics of an FI. The FI-Lab can be applied as a single frailty measure or in combination with/in addition to other frailty instruments.

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“…Az emelkedett LDH a teljes és a daganatspecifikus túlélés független prognosztikai faktorának bizonyult (HR 1,43 [95%-os CI 1,31-1,56], és HR 1,46 [95%-os CI 1,32-1,61]) [100].…”

Section: A Kiindulási Szérum-ldh éS a Rosszindulatú Daganatos Betegekunclassified

A laktátdehidrogenáz (LDH) prognosztikai jelentősége az onkológiában

Deme¹,

Telekes

2017

Orvosi Hetilap

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A rosszindulatú daganatsejtek többségében fokozott a glikolízis, amely biztosítja a proliferációhoz szükséges energia legnagyobb részét. A laktátdehidrogenáz (LDH) anaerob körülmények között katalizálja a reverzibilis piruvát-tejsav átalakulást. A daganatsejtek által expresszált LDHA izoenzim hatására a tejsavképződés jelentősen fokozódik. A tejsav indukálja az oxigenizált daganatsejtek proliferációját, az angiogenezist és gátolja a veleszületett és az adaptív immunválaszt. A szérum-LDH-emelkedés rövidebb túléléssel korrelál. A szerzők áttekintik az LDH-emelkedés és a rosszindulatú daganatos betegségek prognózisa közötti összefüggést feltáró fontosabb vizsgálatokat. Orv Hetil. 2017; 158(50): 1977-1988. Kulcsszavak: laktátdehidrogenáz, rosszindulatú daganatok, prognózis Prognostic importance of lactate dehydrogenase (LDH) in oncologyGlycolysis is increased in most of the malignant cells, providing the largest proportion of energy needed for cell proliferation. Lactate dehydrogenase (LDH) catalyses the reversible process of pyruvate to lactate in anaerobic condition. LDHA isoenzyme expressed mainly by malignant cells, significantly increases lactate formation. Lactate induces the proliferation of oxygenated malignant cells, angiogenesis, and inhibits the innate and adaptive immune responses. Baseline serum LDH elevation correlates with shorter survival. The authors review the relevant studies exploring the correlation between LDH elevation and the prognosis of malignant diseases. Rövidítések A549 = (human non small cell lung cancer cell line A549) humán nem kissejtes tüdőráksejtvonal A549; acetil-CoA = (acetylcoenzyme A) acetil-koenzim A; Acr = activity-regulated cytoskeleton-associated protein; AKT = (protein kinase B) proteinkináz-B; AMP = (adenosine monophosphate) adenozin-monofoszfát; AMPK = (adenosine monophosphate-activated protein kinase) adenozin-monofoszfát aktiválta proteinkináz; ARG1 = (L-arginin metabolizing enzyme arginase-1) L-arginin-metabolizáló enzim argináz-1; ATP = (adenosine triphosphate) adenozin-trifoszfát; CAF = (cancer-associated fibroblasts) daganat asszociálta fibroblastok; CD = (cluster of differentation) differenciációs cluster; CRC = (colorectal cancer) vastag-és végbélrák; CRPC = (castration-resistant prostate cancer) kasztrációrezisztens prostatarák; CSS = (cancer specific survival) daganatspecifikus túlélés; CTL = (cytotoxic T-lymphocyte) citotoxikus T-lymphocyta; DFS = (disease-free survival) betegségmentes túlélés; EGFR = (epidermal growth factor receptor) epidermális növekedési faktor receptor; EpH4 = (nontumorigenic mammary epithelial cells) nem daganatos emlőhámsejt; ER = (estrogen receptor) ösztrogénreceptor; ErbB2 = receptor tyrosine kinase erbB-2 (HER-2/Neu); ERK-2 = (extracellular signal-regulated kinase-2) extracelluláris szignál regulálta kináz 2; FH = (fumarate hydratase) fumaráthidra-táz; c-Fos = Finkel-Biskis-Jinkins-osteosarcoma; FX11 = kis molekulájú LDHA-inhibitor; G6PDH = (glucose-6-phos- Keywords

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Serum lactate dehydrogenase and survival following cancer diagnosis

Cited by 80 publications

References 48 publications

Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion

Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion

Operationalizing a frailty index using routine blood and urine tests

A laktátdehidrogenáz (LDH) prognosztikai jelentősége az onkológiában

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