Elevated Serum Neuron-specific Enolase Research Articles

Cerebrospinal Fluid and Serum Biomarker Insights in Aneurysmal Subarachnoid Haemorrhage: Navigating the Brain-Heart Interrelationship for Improved Patient Outcomes.

The pathophysiological mechanisms underlying severe cardiac dysfunction after aneurysmal subarachnoid haemorrhage (aSAH) remain poorly understood. In the present study, we focused on two categories of contributing factors describing the brain-heart relationship. The first group includes brain-specific cerebrospinal fluid (CSF) and serum biomarkers, as well as cardiac-specific biomarkers. The secondary category encompasses parameters associated with cerebral autoregulation and the autonomic nervous system. A group of 15 aSAH patients were included in the analysis. Severe cardiac complications were diagnosed in seven (47%) of patients. In the whole population, a significant correlation was observed between CSF S100 calcium-binding protein B (S100B) and brain natriuretic peptide (BNP) (rS = 0.62; p = 0.040). Additionally, we identified a significant correlation between CSF neuron-specific enolase (NSE) with cardiac troponin I (rS = 0.57; p = 0.025) and BNP (rS = 0.66; p = 0.029), as well as between CSF tau protein and BNP (rS = 0.78; p = 0.039). Patients experiencing severe cardiac complications exhibited notably higher levels of serum tau protein at day 1 (0.21 ± 0.23 [ng/mL]) compared to those without severe cardiac complications (0.03 ± 0.04 [ng/mL]); p = 0.009. Impaired cerebral autoregulation was noted in patients both with and without severe cardiac complications. Elevated serum NSE at day 1 was related to impaired cerebral autoregulation (rS = 0.90; p = 0.037). On the first day, a substantial, reciprocal correlation between heart rate variability low-to-high frequency ratio (HRV LF/HF) and both GFAP (rS = -0.83; p = 0.004) and S100B (rS = -0.83; p = 0.004) was observed. Cardiac and brain-specific biomarkers hold the potential to assist clinicians in providing timely insights into cardiac complications, and therefore they contribute to the prognosis of outcomes.

The relationship between neuron-specific enolase, high sensitivity C reactive protein, and diabetic peripheral neuropathy in Chinese patients with type 2 diabetes: A prospective nested case–control analysis

BackgroundDiabetic peripheral neuropathy (DPN) involves a very complex pathogenesis, and there is no neuro-specific marker for risk prediction. Neuron-specific enolase (NSE), a key enzyme in glycolysis, has a broad spectrum neurotrophic and neuroprotective effect on neurons, and also cause injury and inflammatory response of peripheral nerves. The relationship between neuron-specific enolase, highly sensitive c-reactive protein (hsCRP), and diabetic peripheral neuropathy remains unclear. We aimed to investigate whether elevated serum NSE and hsCRP levels increased the risk of DPN in patients with type 2 diabetes.Materials and methodsIn this prospective nested case–control study, a total of 1072 eligible subjects with type 2 diabetes constituted the follow-up cohort. Demographic data and parameters including serum NSE and hsCRP were collected at baseline. Two neuropathy screening scales (MNSI and MDNS) were used to assess DPN during follow-up period. Nerve conduction studies were performed at the end of follow-up. Conditional logistic regression was used to inspect the risk factors of the incidence of DPN.ResultsDuring an average follow-up period of 5.1 years, 176 subjects developed DPN. Serum NSE and hsCRP levels at baseline were significantly higher in DPN group than in matched non-DPN groups (p < 0.001). NSE was positively correlated with age and hsCRP (p < 0.001). The amplitude of sensory nerve action potential and compound muscle action potential of the lower extremity nerves were significantly decreased in the high tertile of NSE. After adjustment for matching and confusing factor, conditional logistic regression showed the risk of DPN in the high tertile of NSE level was still 3.176 times higher than that in the low tertile of NSE level (p < 0.001).ConclusionElevated serum NSE levels predicted the high incidence of DPN in Chinese patients with type 2 diabetes for an average of 5.1 years, which may be associated with increased neuroinflammatory response caused by high NSE levels, but further studies are needed.

Role of Neuron-Specific Enolase in the Diagnosis and Disease Monitoring of Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The diagnosis of sarcoidosis is based on clinicopathologic findings accompanied by the formation of granulomas in multiple organs, including the lung. Although angiotensin-converting enzyme (ACE) and soluble interleukin 2 receptor (sIL-2R) are traditionally used for the diagnosis of sarcoidosis, specific diagnostic markers remain to be determined. In the current study, we found that serum neuron-specific enolase (NSE) levels were elevated in patients with sarcoidosis. Serum NSE levels were positively correlated with serum ACE and sIL-2R levels. The sensitivity of NSE alone was modest, but its combination with sIL-2R and ACE had the highest sensitivity compared to those of each single marker. When comparing serum NSE and pro-gastrin-releasing peptide (ProGRP) levels in SCLC patients with those in patients with sarcoidosis and nonsarcoidotic benign diseases, serum NSE could be used to distinguish SCLC from sarcoidosis and nonsarcoidosis by setting at a cutoff value of 17.0 ng/ml with a sensitivity of 73.5% and a specificity of 90.2%, which were comparable to those of ProGRP. Serum NSE levels were associated with organ involvement and were higher in sarcoidosis patients who had been treated with oral corticosteroid (OCS) than in those who had never received OCS therapies; there was a positive association between elevated serum NSE levels and OCS use. Increased concentrations of serum NSE in patients at the nonremission phase decreased after spontaneous remission, whereas serum NSE levels fluctuated in accordance with serum ACE or sIL-2R levels during the follow-up period in patients with sarcoidosis. These findings suggest that NSE could be a marker for the diagnosis and monitoring of the clinical outcome of patients with sarcoidosis.

Serum Neuron-Specific Enolase Levels Associated with Connectivity Alterations in Anterior Default Mode Network after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most prevalent neurological insult and leads to long-lasting cognitive impairment. Neuroimaging studies have discovered abnormalities in brain network connectivity following mTBI as the underlying neural basis of cognitive deficits. However, the pathophysiologic mechanisms involved in imaging alterations remain elusive. Proteins neuron-specific enolase (NSE) and ubiquitin C terminal hydrolase 1 are reliable markers for neuronal cell-body damage, both of which have been demonstrated to be increased in serum following mTBI. Therefore, we conducted a longitudinal study to examine relationships between abnormal brain network connectivity and serum neuronal biomarkers and their associations with cognitive recovery following mTBI. Sixty patients were followed-up at 1 week and 3 months post-injury and 41 controls were recruited. Resting-state functional magnetic resonance imaging was used to build a functional connectivity matrix within large-scale intrinsic networks, and their topological properties were analyzed using graph theory measures. We found that, compared with controls, mTBI patients showed significant decreases in a number of nodal characteristics in default mode network (DMN), salience network, and executive network (p < 0.05, false discovery rate corrected) at 3 months post-injury. Linear regression analysis found elevated serum NSE in acute phase could predict lower efficiency and degree centrality of anterior DMN at 3 months post-injury. In addition, efficiency and degree centrality of anterior DMN were negatively associated with working memory. Our study showed neuronal injury was associated with alterations in brain network connectivity after mTBI. These findings can facilitate capability to predict the brain functional outcomes and cognitive recovery in mTBI.

Significance of serum neuron-specific enolase in transient global amnesia

Neuron-specific enolase (NSE) is a glycolytic enzyme, which is associated with neuronal cell dysfunction in the brain. This study evaluated the role of serum NSE levels of patients with transient global amnesia (TGA). In addition, the relationship between serum NSE levels and the clinical features of TGA was explored. Forty-eight patients with TGA were prospectively included, and their serum NSE levels were measured. We investigated serum NSE levels in patients with TGA. In addition, we analyzed the differences in clinical characteristics between patients with elevated and normal serum NSE levels. Of the 48 patients with TGA, 16 patients (33.3%) had elevated serum NSE levels (25.0 ± 11.5 ng/mL), whereas 32 patients (66.7%) showed normal serum NSE levels (12.8 ± 2.1 ng/mL). The patients with elevated serum NSE levels exhibited higher levels of cognitive impairment than those with normal serum NSE levels (4/16 vs. 1/32, p = 0.036). The serum NSE levels showed a relatively high discrimination (AUC 0.684) between patients with and without cognitive impairment, with 80.0% sensitivity and 74.4% specificity at a cut-off value 17.3 ng/mL. A third of all patients with TGA carry elevated serum NSE levels, which suggests that the neuronal cell dysfunction could be associated with TGA pathogenesis. In addition, it might be correlated with cognitive impairment.

The prognostic biomarkers of the patients treated with platinum-based chemotherapy in treatment emergent or related neuroendocrine prostate cancer.

e17576 Background: Treatment emergent or related neuroendocrine prostate cancer (tNEPC) is an aggressive subtype of prostate cancer in patients previously treated with androgen receptor pathway inhibitor (ARPI) as a mechanism of resistance. These patients are typically treated platinum-based chemotherapy using small cell lung cancer (SCLC). The clinical features of tNEPC are poorly defined. The aim of the present study was to investigate the prognostic biomarkers of the patients treated with platinum-based chemotherapy in tNEPC. Methods: We reviewed baseline, treatment and outcome data of 41 patients with tNEPC. Clinicopathological factors and laboratory data before administering the first cycle of platinum-based chemotherapy were collected to assess the prognostic factors for overall survival (OS). Definition of tNEPC were based on NEPC morphology on the basis of any current or prior tissue sample, development of liver metastases in the absent of PSA progression, or elevated serum neuron specific enolase (NSE). Results: Median PSA and NSE were 119.8 ng/ml and 18.2 ng/ml, respectively. Twenty-four patients had pathologic features of NEPC. NSE were elevated above the 32 patients. The median OS from the start of platinum-based chemotherapy treatment was 10 months. Univariate analysis revealed that LDH (p = 0.003), absolute monocyte count &lt; 280 (p = 0.022), visceral metastasis (p = 0.014) prior to platinum-based chemotherapy were significantly associated with shorter OS. Multivariate analysis revealed that LDH (p = 0.047), absolute monocyte count &lt; 280, (p = 0.012), visceral metastasis (p = 0.005) prior to platinum-based chemotherapy treatment were independent prognostic indicators for OS. Based on the relative risk of death, NEPC patients before platinum-based chemotherapy were divided into 3 risk groups: low, intermediate and high ( p&lt; 0.001). Conclusions: Our findings provide new insights into the practical implication of NEPC. Our results might be to tailor the management of NEPC treated with platinum-based chemotherapy.

Neonatal neuron specific enolase, a sensitive biochemical marker of neuronal damage, is increased in preeclampsia: A retrospective cohort study

BackgroundPreeclampsia leads to chronic intrauterine hypoxia by interfering with placental blood supply. We aimed to investigate whether preeclampsia exposure has an influence on central nervous system of infants, as evaluated by analyzing neonatal serum neuron specific enolase (NSE). MethodsThis was a retrospective study including infants born in Nanfang hospital between Jan 2018 and Feb 2019 without asphyxia. They were divided into normotensive control group and preeclampsia group to compare the NSE levels. Furthermore, PE group was divided into five subgroups by lipstick of urine protein from 0 to 4+ to examine the relationship between urine protein and neonatal NSE. ResultsOf the 86 selected neonates, there were 40 in control group and 46 in preeclampsia group. The NSE levels were significantly higher in infants with preeclampsia exposure compared to those infants in control group (45.504 ± 17.926 vs 30.690 ± 4.475, P < 0.0001). Multiple regression analyses revealed that the preeclampsia (β coef = 0.394, p = 0.041), 4+ proteinuria (β coef = 0.558, p < 0.0001) and 3+ proteinuria (β coef = 0.356, p = 0.005) were significant independent variables predicting elevated serum NSE concentration. ConclusionFor the first time, this research has suggested the increase of neonatal NSE in preeclampsia, and the quantity of maternal proteinuria may be able to predict neonatal NSE elevation. Long-term neurodevelopmental follow-up and targeted preventive strategies are advised for this underrecognized high-risk population.

The effect of obstructive sleep apnea syndrome on serum S100B and NSE levels: a systematic review and meta-analysis of observational studies

BackgroundObstructive sleep apnea syndrome (OSAS) is a common disorder that is accompanied by structural brain changes. This meta-analysis aimed to evaluate the effect of OSAS on the serum levels of astrocytic protein (S100B) and neuron-specific enolase (NSE) in observational studies.MethodsA comprehensive search was performed in the PubMed/Medline, Web of Science, Scopus, ScienceDirect, and Cochrane Library databases to assess the serum level of S100B and/or NSE in patients with OSAS and/or controls. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using RevMan 5.3 with the mean difference (MD) and 95% confidence intervals (CIs).ResultsOut of 63 studies found in the mentioned databases and one identified by a manual search, nine studies were included and analyzed in this meta-analysis (three cross-sectional and six case-control studies). The analysis showed that the S100B [MD = 53.58 pg/ml, 95%CI: 1.81, 105.35; P = 0.04] and NSE levels [MD = 3.78 ng/ml, 95%CI: 2.07, 5.48; P < 0.0001] were significantly higher in patients than the controls. However, there were no significant differences between the S100B [MD = -28.00 pg/ml, 95%CI: − 79.48, 23.47; P = 0.29] and NSE levels [MD = 0.49 ng/ml, 95%CI: − 0.82, 1.80; P = 0.46].ConclusionsThis meta-analysis found elevated serum S100B and NSE levels in OSAS patients compared to the controls, which suggests that these markers may be used as peripheral indicators of brain damage in OSAS.

Distribution of serum neuron-specific enolase and the establishment of a population reference interval in healthy adults.

BackgroundNeuron‐specific enolase (NSE) is an important tumor marker in the serum of patients with lung cancer. Elevated serum NSE levels are also associated with many other diseases. However, there is no unified population reference interval for serum NSE. This study aimed to investigate the distribution of serum NSE in healthy Chinese adults aged 20‐79 years and to establish its reference interval in Chinese population.MethodsA total of 10 575 healthy subjects were in line with the requirements of this study. The concentration of serum NSE was detected by a fully automated Cobas e602 analyzer with matching reagents. The population reference interval for serum NSE was established using the unilateral 95th percentile (P 95) according to standard guidelines.ResultsThe distributions of serum NSE were not significantly different between males and females (P > 0.05) and also did not differ by age (P > 0.05). Therefore, the population reference interval for serum NSE was established as upper limit 25.4 ng/mL (90% confidence interval: 24.5‐26.2 ng/mL).ConclusionsWe established the first population reference interval for serum NSE in a large healthy Chinese adult cohort, which was higher than that recommended by Roche Diagnostics GmbH. This new reference interval is more practical and applicable in Chinese adults.

Inhibition of the PI3K/Akt signaling pathway impedes the restoration of neurological function following hypoxic-ischemic brain damage in a neonatal rabbit model.

Hypoxic-ischemic brain damage (HIBD), frequently occurring in infancy and childhood, is a major cause of mortality and severe neurologic impairment. This study was performed to examine the effect of the PI3K/Akt signaling pathway on HIBD in a neonatal rabbit model. Uterine artery occlusion was used to establish HIBD models in neonatal rabbits, which were then subjected to sham operation, dimethyl sulfoxide (2 mL) or LY294002 (inhibitor of PI3K/Akt signaling pathway, 6.4 μg/kg). Behavioral neurological assessment was performed in neonatal rabbits delivered by cesarean section, after which serum neuron-specific enolase (NSE) level and cerebral water content were determined. The level of cleaved caspase-3 level and apoptosis of neurons were observed by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, the expression of PI3K/Akt signaling pathway- and apoptosis-related factors was examined. In neonatal rabbits, HIBD increased the fetal death rate; reduced neurological scores of posture, righting reflex, and deglutition reflex; elevated serum NSE levels, cerebral water content, cleaved caspase-3-positive expression in hippocampal CA1 region and apoptotic neurons; inactivated PI3K/Akt signaling pathway as well as reduced Bcl-2 expression and increased BAD and Bax expression. Notably, the treatment of LY294002 further aggravated neurological impairment in neonatal rabbits in response to HIBD. Following the HIBD caused by intrauterine asphyxia, the LY294002 administered through auricular vein infusion into pregnant rabbits exacerbates neurological impairment of neonatal rabbits, suggesting that inhibition of PI3K/Akt signaling pathway may serve as a candidate therapeutic target for neurological recovery.

Right Lung Consolidation Combined Elevated Serum Neuron Specific Enolase Misdiagnosed as Lung Carcinoma Ultimately Confirmed Pulmonary Cryptococcosis by CT-guided Percutaneous Lung Biopsy: a Case Report and Literature Review

Detection of serum neuron specific enolase (NSE) has high sensitivity and specificity in the diagnosis of lung carcinoma, especially in small cell lung carcinoma, but sometimes serum NSE provided limited help. We report a case of a patient with right lung consolidation combined with elevated serum neuron specific enolase which mimicked lung carcinoma and was ultimately confirmed as pulmonary cryptococcosis by CT-guided percutaneous lung biopsy. Chest computed tomography (CT) scan and CT-guided percutaneous lung biopsy were performed for diagnosis and blood tests explored the latent etiology. The chest CT scan showed right lung consolidation and a pulmonary nodule in lingual segment of upper lobe of left (Figure1A - F). Serum cryptococcal antigen was positive. Pathology of CT-guided percutaneous lung biopsy confirmed pulmonary cryptococcosis (Figure 1G - I). Elevated NSE is not a specific index of lung cancer. Serum cryptococcal antigen and CT-guided percutaneous lung biopsy has high specificity in cryptococcal pneumonia.

Prognostic Significance of Neuron-Specific Enolase in Patients with Malignant Lymphoma

[Introduction] Neuron-specific enolase (NSE) is the γ-γ or γ-δ dimer isoenzyme of enolase, an acidic protease that promotes the conversion of β-glycerophosphate into dihydroxyacetone phosphate during glycolysis, is mainly found in mature neurons and cells of neuronal origin. Studies of NSE as a tumor marker have primarily focused on patients with small cell lung cancer and neuroblastoma. NSE is not only a useful marker for disease aggressiveness, but also a prognostic factor. Elevated serum NSE expression has been found in 35% of non-neuroendocrine tumors, such as non-small cell lung carcinoma, breast cancer, and multiple myeloma. However, few reports have indicated whether serum NSE levels influence the clinical features and prognosis of malignant lymphoma (ML). In this study, we analyzed the serum NSE levels of patients with newly diagnosed ML and investigated their correlation with clinical outcomes.[Methods] We retrospectively analyzed 187 patients with ML diagnosed at our institution between 2011 and 2017. The patients included 109 males and 78 females with a median age of 72 years (range 22-93 years). The histological subtypes were; 93 DLBCL, 42 FL, 9 MALT, 7 MCL, 5 BL, 12 PTCL, 12 HL, and others. The study protocol was approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki.[Results] Median follow-up time was 38 months. The mean serum value of NSE in 187 lymphoma patients was 23.77+/- 36.04 ng/ml. The mean NSE value in 93 DLBCL patients was significantly higher than that in 42 FL patients (26.99+/-27.56 ng/ml versus 13.80+/-6.85 ng/ml, respectively; p=0.003). Among 93 DLBCL patients, the optimal serum NSE cutoff value for predicting 3-year survival was determined by ROC analysis to be 17.1 ng/ml. In DLBCL patients, patients with high serum NSE levels (≥17.1 ng/ml; N=40) had significantly shorter overall survival (OS) than those with low serum NSE levels (<17.1 ng/ml; N=53) (3-year OS, 29.2% versus 70.9%, respectively; p<0.001) (Figure 1). In univariate analysis, parameters having adverse significance for OS were: high serum NSE levels, high serum LDH levels, PS≥2, stage 3-4, and R-IPI poor risk. In multivariate analysis, parameters having independent adverse significance for OS were: high serum NSE levels (≥17.1 ng/ml) (p=0.03, HR 2.04) and PS≥2 (p<0.001, HR 4.82). Among 42 FL patients, patients with high serum NSE levels (N=10) had also shorter OS than those with low serum NSE levels (N=32) (3-year OS, 60.0% versus 85.1%, respectively; p=0.02). The mean NSE value in high-risk FLIPI patients was higher than that in low- or intermediate-risk FLIPI patients (19.36+/-12.02 ng/ml versus 11.89+/-2.44 ng/ml, respectively; p=0.002).[Conclusion] In the present study we demonstrated that serum NSE levels were elevated in patients with various types of lymphoma. In particular, our data proved that a high serum NSE level is an independent prognostic factor for survival in patients with DLBCL. These results suggest that serum NSE levels at diagnosis may have an important role in malignant lymphoma and also may be a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Serial measurement of S100B and NSE in pediatric traumatic brain injury

Increased serum biomakers, such as S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE), are associated with traumatic brain injury (TBI). The purpose of this study is to investigate the serum levels of S100B and NSE in pediatric TBI patients and to predict a clinical outcome. Peripheral venous blood was collected within 6h of injury and at 1week to measure S100B and NSE. The serum S100B and NSE levels were measured using commercially available enzyme-linked immunosorbent assay kits. The authors divided participants into two groups at admission: a favorable group (patients with Glasgow Coma Scale [GCS] scores of 10-15) and an unfavorable group (patients with GCS scores of less than 9). Both S100B and NSE levels were compared between the two groups at the time of admission and 1week later. Ten pediatric patients were enrolled (5 in the favorable group, 5 in the unfavorable group). The median serum S100B level of 134.21pg/ml (range, 51.00-789.65pg/ml) in patients with TBI at admission dropped to 41.49pg/ml (range, 25.65-260.93pg/ml) after 1week, with significant differences between the traumatic event and 1week later (p = 0.007). The median serum NSE level of 14.76ng/ml (range, 6.48-21.23ng/ml) in patients with TBI at admission was higher than that after 1week (4.96ng/ml, range, 3.01-31.21ng/ml), with significant differences (p = 0.015). A significant difference was observed in S100B after 1week between patients in the favorable and unfavorable groups (p = 0.047). One patient whose serum S100B and NSE levels were elevated 1week after TBI eventually died. Elevated serum S100B and NSE levels in pediatric TBI patients decreased 1week after traumatic events. The serum S100B level 1week after TBI was related to the severity of brain damage. These results indicated that serum S100B and NSE might play a role in predicting the prognosis and monitoring ongoing brain injury in pediatric TBI patients.

Peripheral-type small cell lung cancer is associated with better survival and higher frequency of interstitial lung disease

ObjectivesSmall cell lung cancer (SCLC) can be subgrouped into central and peripheral types according to the location of the primary lesion. However, the clinical differences between these two types remain unclear. This study compared their clinical features. Materials and methodsData on 231 patients with pathologically diagnosed SCLC were retrospectively subgrouped into central or peripheral types. Progression-free survival (PFS), overall survival (OS), treatments, responses to first-line therapy, and frequency of interstitial lung disease (ILD) were compared between the two groups. ResultsOf the 231 patients, 101 (44%) had central-type and 130 (56%) had peripheral-type SCLC. Peripheral-type SCLC was associated with a better performance status, higher frequency of ILD, and higher rate of limited disease stage. Patients with peripheral-type SCLC had a significantly longer OS than did those with central-type SCLC (median, 502 vs 370days, respectively; p=0.0186). Tumor location was not associated with PFS. PFS was poorer in patients with than without ILD (median, 143 vs 213days, respectively; p=0.0038), as was OS (median, 245 vs 545days, respectively; p=0.0014). Among patients without ILD, OS was longer in those with peripheral- than central-type tumors (median, 662 vs 421days, respectively; p=0.0074). Surgical resection was more often chosen for peripheral-type tumors, and this was one reason for the prolonged survival. There was no difference in the response to chemotherapy and/or radiotherapy between central- and peripheral-type SCLC. Multivariate analysis by a Cox proportional hazards model showed that male sex, a poor performance status, extensive disease, the presence of ILD, an elevated serum neuron-specific enolase concentration, and central-type SCLC were poor prognostic factors for OS. ConclusionPeripheral-type SCLC is associated with better OS and a higher frequency of ILD than is central-type SCLC. The presence of ILD is a poor prognostic factor for both PFS and OS.

The role of serum neuron-specific enolase in patients with prostate cancer: a systematic review of the recent literature.

In this systematic review, we evaluated the value of serum concentrations of neuron-specific enolase (NSE) in patients with prostate cancer (PCa) in order to clarify the possible role of NSE in the diagnosis, management, treatment and monitoring of PCa. A comprehensive search of the recent literature was conducted to find relevant data on the role of NSE in PCa. Two hundred and eighty-two records were revealed, and 19 articles including 1,772 patients with PCa (either confirmed or suspected) were selected. After reviewing the articles, the major result was that elevated serum NSE appears to correlate with prognosis in advanced PCa, particularly in patients with progressive and metastatic castration-resistant PCa. Based on the existing literature, the role of serum NSE in PCa patients should be further evaluated.

Systematic Correlation Analyses of Circulating Tumor Cells with Clinical Variables and Tumor Markers in Lung Cancer Patients.

Measurement of circulating tumor cells (CTC) offers promise as a clinical biomarker to monitor disease status, therapeutic response, and progression in cancer patients. However, its clinical value in lung cancer patients has not been fully explored. We systematically evaluate the association of CTCs with clinical variables and tumor markers in a cohort of lung cancer patients. Using the CELLSEARCH System, CTCs were detected in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients prior to therapy. Univariate analysis revealed that detection of CTC was related to histology, stage, tumor size, invasiveness, and lymphatic metastasis. CTCs were associated with distant metastases in NSCLC, but not in SCLC. Using multivariate analysis, we found that CTCs were independently correlated with disease stage, SCLC, and elevated serum neuron-specific enolase (NSE). These data suggest that CTCs are more likely to be detected in patients with stage IV disease and with SCLC, and that elevated serum NSE predicts the presence of CTCs.

Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response.

Background/Aims:It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients.Methods:A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence.Results:A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients.Conclusions:Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions.

Serum Neuron-Specific Enolase Levels Predict the Efficacy of First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Patients With Non-Small Cell Lung Cancer Harboring EGFR Mutations

ObjectivesOur study aimed to determine the predictive and prognostic values of the serum neuron-specific enolase (NSE) level in patients who had non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and who had been treated with EGFR-tyrosine kinase inhibitors (TKIs). Materials and MethodsWe retrospectively analyzed 151 patients who had NSCLC harboring EGFR mutations and had received either gefitinib or erlotinib as first-line treatment between 2005 and 2014. The serum NSE level was measured before initiation of EGFR-TKI treatment. ResultsOf the 151 patients, 92 (60.9%) had elevated NSE levels (> 16.3 ng/mL). Patients with elevated NSE levels showed significantly shorter progression-free survival (PFS) after EGFR-TKI treatment than those with normal NSE levels (median PFS, 10.5 months vs. 15.4 months; P = .034). Multivariate analysis demonstrated that elevated NSE levels (hazard ratio [HR], 1.656; P = .017), CNS metastasis at diagnosis (HR, 1.567; P = .037), and male gender (HR, 1.840; P = .005) were independent predictive factors for short PFS. A significant difference in overall survival (OS) was observed between patient groups with elevated and normal NSE levels (median OS, 17.0 months vs. 29.1 months; P < .001), and serum NSE level remained an independent prognostic factor for OS in multivariate analysis (HR, 2.671; P < .001). ConclusionPatients with elevated serum NSE levels have significantly shorter PFS and OS. The NSE level is both a predictive marker of EGFR-TKI treatment and a prognostic marker in EGFR-mutant NSCLC patients.

Changes of serum neuron-specific enolase and serum ferritin levels in patients with pneumoconiosis

To investigate the changes in serum neuron-specific enolase (NSE) and serum ferritin (SF) in patients with pneumoconiosis and their relationship with the onset of pneumoconiosis. The serum NSE and SF levels in the peripheral blood of patients with pneumoconiosis were measured by electrochemical fluorescence immunoassay. The patients with first-stage pneumoconiosis and second-stage pneumoconiosis had significantly higher serum NSE and SF levels than the control group (23.0264±14.0410 and 44.9776±26.5208 ng/ml vs 8.1480±3.7512 ng/ml, P < 0.05; 267.2515±186.5809 and 579.1371±433.9326 ng/ml vs 120.8613±74.2809 ng/ml, P < 0.05), and the patients with second-stage pneumoconiosis had significantly higher serum NSE and SF levels than those with first-stage pneumoconiosis (P < 0.05). After treatment, the serum NSE level decreased significantly in the patients with pneumoconiosis (21.1675±17.5942 ng/ml vs 33.4490±21.6948 ng/ml, P < 0.05), but it was still significantly higher than that in the control group (P < 0.05). The treatment did not produce significant changes in SF level among these patients (P > 0.05). Patients with pneumoconiosis have elevated serum NSE and SF levels, which may be related to the onset and progression of this disease.

Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress. Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation "carriers," 14/74 were "affected," and 14/74 were "off-pedigree" controls. Serum NSE levels were determined by ELISA specific for the γ subunit of NSE. Serum NSE concentrations in carriers (27.17 ± 39.82 μg/L) were significantly higher than affected (5.66 ± 4.19 μg/L; P = 0.050) and off-pedigree controls (6.20 ± 2.35 μg/L; P = 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean = 75.8 ± 42.3 μg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 ± 51.21 μg/L) than in asymptomatic female carriers (15.85 ± 22.27 μg/L; P = 0.034). Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress.