Showing papers in "Disease Markers in 2017"

Long Noncoding RNAs as Biomarkers in Cancer.

Abstract: Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients

Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases.

Abstract: The red blood cell distribution width (RDW) obtained from a standard complete blood count (CBC) is a convenient and inexpensive biochemical parameter representing the variability in size of circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV) has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms.

Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance.

Abstract: Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P < 0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P < 0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P = 0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.

DNA Methylation as a Noninvasive Epigenetic Biomarker for the Detection of Cancer.

Abstract: In light of the high incidence and mortality rates of cancer, early and accurate diagnosis is an important priority for assigning optimal treatment for each individual with suspected illness. Biomarkers are crucial in the screening of patients with a high risk of developing cancer, diagnosing patients with suspicious tumours at the earliest possible stage, establishing an accurate prognosis, and predicting and monitoring the response to specific therapies. Epigenetic alterations are innovative biomarkers for cancer, due to their stability, frequency, and noninvasive accessibility in bodily fluids. Epigenetic modifications are also reversible and potentially useful as therapeutic targets. Despite this, there is still a lack of accurate biomarkers for the conclusive diagnosis of most cancer types; thus, there is a strong need for continued investigation to expand this area of research. In this review, we summarise current knowledge on methylated DNA and its implications in cancer to explore its potential as an epigenetic biomarker to be translated for clinical application. We propose that the identification of biomarkers with higher accuracy and more effective detection methods will enable improved clinical management of patients and the intervention at early-stage disease.

The Role of Hematological Indices in Patients with Acute Coronary Syndrome

Abstract: An increased systemic and local inflammation plays a key role in the pathophysiology of acute coronary syndrome (ACS). This review will discuss the role of hematological indices: white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and platelet indices, that is, platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) in the case of ACS. In recent years, a strong interest has been drawn to these indices, given that they may provide independent information on pathophysiology, risk stratification, and optimal management. Their low-cost and consequent wide and easy availability in daily clinical practice have made them very popular in the laboratory testing. Furthermore, many studies have pointed at their effective prognostic value in all-cause mortality, major cardiovascular events, stent thrombosis, arrhythmias, and myocardial perfusion disorders in terms of acute myocardial infarction and unstable angina. The most recent research also emphasizes their significant value in the combined analysis with other markers, such as troponin, or with GRACE, SYNTAX, and TIMI scores, which improve risk stratification and diagnosis in ACS patients.

LncRNA NEAT1 Regulates Cell Viability and Invasion in Esophageal Squamous Cell Carcinoma through the miR-129/CTBP2 Axis.

Abstract: Background Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be aberrantly upregulated and promote esophageal squamous cell carcinoma (ESCC) cell progression Nevertheless, the molecular mechanism of NEAT1 involved in the competing endogenous RNA (ceRNA) regulatory network in ESCC progression remains poorly defined Methods The expressions of NEAT1, miR-129, and C-terminal-binding protein 2 (CTBP2) in ESCC cells were examined by qRT-PCR The effects of NEAT1 knockdown and miR-129 overexpression, or along with CTBP2 upregulation, on ESCC cell viability and invasion were explored by CCK-8 and transwell invasion assays, respectively Luciferase reporter assay in combination with RIP was performed to confirm the interaction between NEAT1, miR-129, and CTBP2 Results NEAT1 and CTBP2 were upregulated and miR-129 was downregulated in ESCC cells Either NEAT1 knockdown or miR-129 overexpression suppressed ESCC cell viability and invasion Moreover, NEAT1 functioned as an endogenous sponge to downregulate miR-129 by competitively binding to miR-129, thereby leading to the derepression of CTBP2, a target of miR-129 CTBP2 restoration overturned cell viability and invasion suppression mediated by NEAT1 knockdown or miR-129 overexpression Conclusion LncRNA NEAT1 regulated ESCC cell viability and invasion via the miR-129/CTBP2 axis, contributing to the better understanding of the molecular mechanism of ESCC pathogenesis and progression

Growth Differentiation Factor-15 Is a Predictor of Mortality in Critically Ill Patients with Sepsis.

Abstract: Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily related to inflammation and macrophage activation. Serum concentrations of GDF-15 can predict poor survival in chronic diseases, but its role in sepsis is obscure. Therefore, we investigated GDF-15 as a prognostic biomarker in critically ill patients. We measured GDF-15 levels in 219 critically ill patients (146 with sepsis, 73 without sepsis) upon admission to the intensive care unit (ICU), in comparison to 66 healthy controls. GDF-15 levels were significantly increased in ICU patients compared to controls. GDF-15 was further increased in sepsis and showed a strong association with organ dysfunction (kidney, liver and lactate) and disease severity (APACHE II and SOFA score). High GDF-15 concentrations at admission independently predicted ICU (HR 3.42; 95% CI 1.33–8.78) and overall mortality (HR 2.02, 95% CI 1.02–3.88) in all ICU critically ill patients as well as in a large subgroup of sepsis patients (ICU mortality: HR 3.16; 95% CI 1.10–9.07; overall mortality: HR 2.62; 95% CI 1.14–6.02). Collectively, serum GDF-15 levels are significantly increased in critically ill patients, associated with sepsis, organ failure, and disease severity. High GDF-15 levels at ICU admission predict short- and long-term mortality risk.

Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness

Abstract: Arterial stiffness is associated with cardiovascular risk, morbidity, and mortality. The present paper reviews the main vitamins related to arterial stiffness and enabling destiffening, their mechanisms of action, providing a brief description of the latest studies in the area, and their implications for primary cardiovascular prevention, clinical practice, and therapy. Despite inconsistent evidence for destiffening induced by vitamin supplementation in several randomized clinical trials, positive results were obtained in specific populations. The main mechanisms are related to antiatherogenic effects, improvement of endothelial function (vitamins A, C, D, and E) and metabolic profile (vitamins A, B12, C, D, and K), inhibition of the renin-angiotensin-aldosterone system (vitamin D), anti-inflammatory (vitamins A, D, E, and K) and antioxidant effects (vitamins A, C, and E), decrease of homocysteine level (vitamin B12), and reversing calcification of arteries (vitamin K). Vitamins A, B12, C, D, E, and K status is important in evaluating cardiovascular risk, and vitamin supplementation may be an effective, individualized, and inexpensive destiffening therapy.

Predictive Value of MiR-219-1, MiR-938, MiR-34b/c, and MiR-218 Polymorphisms for Gastric Cancer Susceptibility and Prognosis.

Abstract: Gastric cancer (GC) is one of the most prominent global cancer-related health threats. Genes play a key role in the precise mechanisms of gastric cancer. SNPs in mi-RNAs could affect mRNA expression and then affect the risk and prognosis of GC. Firstly, we have decided to perform a case-control study which included 897 GC patients and 992 controls to evaluate the association of miR-219-1 rs213210, miR-938 rs2505901, miR-34b/c rs4938723, and miR-218 rs11134527 polymorphisms with gastric cancer susceptibility. Secondly, among the 897 GC patients above, 755 cases underwent a radical operation, without distant metastasis and with negative surgical margins included in the survival analysis to evaluate the association of the four SNPs above with gastric cancer prognosis. The C/T or C/C genotypes of rs213210 were related to a lower GC risk (OR = 0.76, 95% CI: 0.62–0.93, ) compared to the T/T genotype. Rs11134527 in miR-218 was associated with GC survival, and the G/A and G/G genotypes of rs11134527 resulted in a decreased risk of death when compared with the A/A genotype (HR = 0.75, 95% CI: 0.61–0.95, ). This study found that miR-219-1 rs213210 polymorphism was associated with GC susceptibility and rs11134527 in miR-218 was positively correlated with GC prognosis.

Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients.

Abstract: Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n = 207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n = 91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5) in all histological types, where miR-1274A (tRNALys5) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.

Circulating Th1, Th2, and Th17 Levels in Hypertensive Patients

Abstract: Background. Evidence from experimental studies showed that Th1, Th2, and Th17 play a pivotal role in hypertension and target organ damage. However, whether changes in the circulating Th1, Th2, and Th17 levels are associated with nondipper hypertension and carotid atherosclerotic plaque in hypertension has yet to be investigated. Methods. Th1, Th2, and Th17 levels were detected using a flow cytometric analysis, and their related cytokines were measured by enzyme-linked immunosorbent assay in 45 hypertensive patients and 15 normotensive subjects. Results. The frequencies of Th1 and Th17 in hypertensive patients, especially in nondipper patients and patients with carotid atherosclerotic plaque, were markedly higher than those in the control group; this was accompanied by higher IFN-γ and IL-17 levels. In contrast, the Th2 frequencies and IL-4 levels in hypertensive patients, especially in nondipper patients and patients with carotid atherosclerotic plaque, were significantly lower than those in the control group. Conclusions. The changes in Th1, Th2, and Th17 activity are associated with the onset of the nondipper type and carotid atherosclerotic plaque in hypertensive patients.

An Elevated Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Colorectal Cancer: A Meta-Analysis

Abstract: Background. The aims of this study were to evaluate the clinicopathological and prognostic values of platelet-to-lymphocyte ratio (PLR) in colorectal cancer (CRC). Methods. The PubMed and Embase databases and the references of relevant studies were systematically searched. This study was performed with hazard ratios (HRs) and odd ratios (ORs) with corresponding 95% confidence intervals (CIs) as effect measures. Results. Our results indicated that elevated PLR was associated with poor overall survival (HR = 1.46, 95% CI = 1.23–1.73), disease-free survival (HR = 1.64, 95% CI = 1.17–2.30), cancer-specific survival (HR = 1.30, 95% CI = 1.12–1.51), and recurrence-free survival (HR = 1.38, 95% CI = 1.09–1.74) in CRC. For the clinicopathological characteristics, our results indicated that there were differences in the rate of elevated PLR between stages III/IV and I/II groups (OR = 1.38, 95% CI = 1.01–1.88), pT3/T4 and pT1/T2 groups (OR = 1.82, 95% CI = 1.03–3.20), and poor differentiation and moderate/well differentiation (OR = 2.59, 95% CI = 1.38–4.84). Conclusions. Our results indicated that elevated PLR predicted poor prognosis and clinicopathological characteristics in CRC and PLR is a convenient and low-cost blood-derived prognostic marker for CRC.

Metabolic Footprints and Molecular Subtypes in Breast Cancer.

Abstract: Cancer treatment options are increasing. However, even among the same tumor histotype, interpatient tumor heterogeneity should be considered for best therapeutic result. Metabolomics represents the last addition to promising "omic" sciences such as genomics, transcriptomics, and proteomics. Biochemical transformation processes underlying energy production and biosynthetic processes have been recognized as a hallmark of the cancer cell and hold a promise to build a bridge between genotype and phenotype. Since breast tumors represent a collection of different diseases, understanding metabolic differences between molecular subtypes offers a way to identify new subtype-specific treatment strategies, especially if metabolite changes are evaluated in the broader context of the network of enzymatic reactions and pathways. Here, after a brief overview of the literature, original metabolomics data in a series of 92 primary breast cancer patients undergoing surgery at the Istituto Nazionale dei Tumori of Milano are reported highlighting a series of metabolic differences across various molecular subtypes. In particular, the difficult-to-treat luminal B subgroup represents a tumor type which preferentially relies on fatty acids for energy, whereas HER2 and basal-like ones show prevalently alterations in glucose/glutamine metabolism.

Validation of a Machine Learning Approach for Venous Thromboembolism Risk Prediction in Oncology

Abstract: Using kernel machine learning (ML) and random optimization (RO) techniques, we recently developed a set of venous thromboembolism (VTE) risk predictors, which could be useful to devise a web interface for VTE risk stratification in chemotherapy-treated cancer patients. This study was designed to validate a model incorporating the two best predictors and to compare their combined performance with that of the currently recommended Khorana score (KS). Age, sex, tumor site/stage, hematological attributes, blood lipids, glycemic indexes, liver and kidney function, BMI, performance status, and supportive and anticancer drugs of 608 cancer outpatients were all entered in the model, with numerical attributes analyzed as continuous values. VTE rate was 7.1%. The VTE risk prediction performance of the combined model resulted in 2.30 positive likelihood ratio (+LR), 0.46 negative LR (-LR), and 4.88 HR (95% CI: 2.54-9.37), with a significant improvement over the KS [HR 1.73 (95% CI: 0.47-6.37)]. These results confirm that a ML approach might be of clinical value for VTE risk stratification in chemotherapy-treated cancer outpatients and suggest that the ML-RO model proposed could be useful to design a web service able to provide physicians with a graphical interface helping in the critical phase of decision making.

Longitudinal Assessment of Transorbital Sonography, Visual Acuity, and Biomarkers for Inflammation and Axonal Injury in Optic Neuritis.

Abstract: Background and Objective. To investigate the relationship between optic nerve sheath diameter, optic nerve diameter, visual acuity and osteopontin, and neurofilament heavy chain in patients with acute optic neuritis. Patients and Methods. Sonographic and visual acuity assessment and biomarker measurements were executed in 23 patients with unilateral optic neuritis and in 19 sex- and age-matched healthy controls. Results. ONSD was thicker on the affected side at symptom onset (median 6.3 mm; interquartile range 6.0–6.5) than after 12 months (5.3 mm; 4.9–5.6; ) or than in controls (5.2 mm; 4.8–5.5; ). OND was significantly increased in the affected side (3.4 mm; 2.9–3.8) compared to healthy controls (2.7 mm; 2.5–2.9; ) and was thicker at baseline than after 12 months (2.8 mm; 2.7–3.0; ). Visual acuity improved significantly after 12 months (1.00; 0.90–1.00) compared to onset of symptoms (0.80; 0.40–1.00; ). OPN levels were significantly higher in patients at presentation (median 6.44 ng/ml; 2.05–10.06) compared to healthy controls (3.21 ng/ml, 1.34–4.34; ). Concentrations of NfH were significantly higher in patients than in controls. Conclusion. ONSD and OND are increased in the affected eye. OPN and NfH are elevated in patients, confirming the presence of any underlying inflammation and axonal injury.

Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma.

Abstract: The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance.

Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis?

Abstract: Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes. Early diagnosis and accurate prognostication remain problematic. BAP1 is a tumour suppressor gene commonly mutated in MM. Germline BAP1 mutation has been associated with early onset and less aggressive disease compared with sporadic MM. Sporadic BAP1 mutations are common and are associated with improved survival in MM, contrary to other malignancies. This study investigated the prognostic role of BAP1 in matched cytology and surgical specimens and aimed to investigate the association between BAP1 and the established prognostic marker VEGFA from a cohort of 81 patients. BAP1 mutation was found in 58% of histology and 59% of cytology specimens. Loss of BAP1 expression in both surgical and cytology specimens was significantly associated with poorer survival in a multivariate analysis when controlling for known prognostic indicators. Increased levels of VEGFA in pleural effusions were associated with poor survival. We conclude that the prognostic significance of BAP1 mutations in MM cannot be determined in isolation of other prognostic factors, which may vary between patients. Pathologists should employ caution when commenting on prognostic implications of BAP1 status of MM patients in diagnostic pathology reports, but it may be useful for early diagnosis.

MicroRNAs Involvement in Radioresistance of Head and Neck Cancer.

Abstract: Resistance to the ionizing radiation is a current problem in the treatment and clinical management of various cancers including head and neck cancer. There are several biological and molecular mechanisms described to be responsible for resistance of the tumors to radiotherapy. Among them, the main mechanisms include alterations in intracellular pathways involved in DNA damage and repair, apoptosis, proliferation, and angiogenesis. It has been found that regulation of these complex processes is often controlled by microRNAs. MicroRNAs are short endogenous RNA molecules that posttranscriptionally modulate gene expression and their deregulated expression has been observed in many tumors including head and neck cancer. Specific expression patterns of microRNAs have also been shown to predict prognosis and therapeutic response in head and neck cancer. Therefore, microRNAs present promising biomarkers and therapeutic targets that might overcome resistance to radiation and improve prognosis of head and neck cancer patients. In this review, we summarize the current knowledge of the functional role of microRNAs in radioresistance of cancer with special focus on head and neck cancer.

EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs.

Abstract: High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications Hence, new biomarkers for HGSOC are urgently required This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein

Biomarkers of Cardiovascular Disease

Abstract: The first € price and the £ and $ price are net prices, subject to local VAT. Prices indicated with * include VAT for books; the €(D) includes 7% for Germany, the €(A) includes 10% for Austria. Prices indicated with ** include VAT for electronic products; 19% for Germany, 20% for Austria. All prices exclusive of carriage charges. Prices and other details are subject to change without notice. All errors and omissions excepted. V.B. Patel, V.R. Preedy (Eds.) Biomarkers in Cardiovascular Disease

Purple Urine Bag Syndrome: A Rare Spot Diagnosis

Abstract: Purple urine bag syndrome (PUBS) is a complication of urinary tract infections (UTIs) where catheter bags and tubing turn purple. It is alarming for patients, families, and clinicians; however, it is in itself a benign phenomenon. PUBS is the result of UTIs with specific bacteria that produce sulphatases and phosphatases which lead tryptophan metabolism to produce indigo (blue) and indirubin (red) pigments, a mixture of which becomes purple. Risk factors include female gender, immobility, constipation, chronic catheterisation, and renal disease. Management involves reassurance, antibiotics, and regular changing of catheters, although there are debates regarding how aggressively to treat and no official guidelines. Prognosis is good, but PUBS is associated with high morbidity and mortality due to the backgrounds of patients. Here, we review the literature available on PUBS, present a summary of case studies from the last five years, and propose the Oxford Urine Chart as a tool to aid such diagnoses.

Near-Infrared Spectroscopy Reveals Abnormal Hemodynamics in the Left Dorsolateral Prefrontal Cortex of Menopausal Depression Patients

Abstract: Background/Objective. Menopausal depression (MD) is characterized by depressive symptoms along with hormonal fluctuations. We investigate brain function alteration between major depressive disorder (MDD) and MD. Methods. The difference in oxygenated hemoglobin (Oxy-Hb) for the prefrontal cortex (PFC) was compared retrospectively among 90 females presented with 30 MDD, 30 MD, and 30 healthy controls (HCs) using verbal fluency task (VFT) with near-infrared spectroscopy (NIRS). Results. We observed a significant difference in Oxy-Hb alteration in the left dorsolateral PFC (DLPFC) using VFT with NIRS (channel 18, ) between the MD and MDD groups. A significant difference in Oxy-Hb levels was observed among the three groups in the bilateral DLPFC (channels 18, 27, 33, 39, 41, and 45; ). Compared to the HCs, the MD group presented lower Oxy-Hb activation in the right DLPFC (channel 41; ) and the left DLPFC (channels 18, 39, and 45; ), and the MDD group presented lower Oxy-Hb activation in the right DLPFC (channels 27, 33, and 41; ) and the left DLPFC (channels 39 and 45; ). Conclusion. Abnormal hemodynamics of the left DLPFC can differentiate MD from MDD by NIRS.

Diagnostic Value of the lncRNA NEAT1 in Peripheral Blood Mononuclear Cells of Patients with Sepsis

Abstract: Background. This study aims to evaluate the diagnostic value of nuclear-enriched abundant transcript 1 (NEAT1) expression in peripheral blood mononuclear cells (PBMCs) for the early diagnosis of sepsis. Methods. A total of 59 patients with sepsis, 52 noninfectious SIRS patients, and 56 healthy controls were recruited fort this study. The levels of NEAT1 expression in PBMCs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Results. Compared with healthy controls, NEAT1 expression of PBMCs in sepsis and SIRS groups were significantly increased (3.76 ± 0.71- and 1.64 ± 0.43-fold, resp.) ( ), but NEAT1 levels are significantly lower in the SIRS group than in the sepsis group, and there was no statistical significant relevance between survivors and nonsurvivors in patients with sepsis. NEAT1 with an area under the curve (AUC) of 0.851 (95% CI: 0.812–0.935) indicated sensitivity (67.85%) and specificity (87.27%) for the diagnosis for sepsis, the positive predictive value (PPV) was 83.3%, and the negative predictive value (NPV) was 71.6%. The AUC for NEAT1 in the diagnosis of SIRS versus healthy controls was 0.755 (95% CI: 0.664–0.847), with 69.23% sensitivity and 70.91% specificity, the PPV was 72.3%, and the NPV was 72.49%. Conclusion. Measurement of NEAT1 expression in PBMCs could be considered as a good additive marker for the diagnosis of sepsis.

Circulating Tumor Cells Were Associated with the Number of T Lymphocyte Subsets and NK Cells in Peripheral Blood in Advanced Non-Small-Cell Lung Cancer.

Abstract: In this study, we aim to investigate the correlation between circulating tumor cells (CTCs) and the T lymphocyte subsets and NK cells in peripheral blood in non-small-cell lung cancer (NSCLC). The peripheral blood CTCs were determined by SET-iFISH. Flow cytometry was used to determine the distribution of T lymphocyte subsets and NK cells. Forty-one (49%) patients showed positivity for CTCs. Logistic regression analysis revealed CTC number was negatively correlated with the ratio of CD3+, CD4+, CD4+/CD8+, and NK % in patients at stage IV, while in a positive correlation was noticed between CTC number and regulatory T cell (Tregs) ratio in these patients. Multivariate analysis was performed in combination with the clinical-pathological materials to identify the risk factors for CTC positivity. Differentiation, NSCLC stage, percentages of CD3+CD4+ cells, Tregs, and NK cells were the independent risk factors for CTCs. CTCs were associated with the decrease of immune surveillance in the peripheral blood in NSCLC patients. The decrease of immune surveillance contributed to the escape of CTCs from the killing effects of the immunocytes, as well as the formation of metastasized lesions in the target organs.

Identification of Circulating Long Noncoding RNA Linc00152 as a Novel Biomarker for Diagnosis and Monitoring of Non-Small-Cell Lung Cancer

Abstract: Objective. Long noncoding RNAs (lncRNAs) have been reported to play vital roles in non-small-cell lung cancer (NSCLC). Recently, long noncoding RNA Linc00152 has been reported to play important roles in various cancers. In this study, our aim was to investigate its expression pattern and clinical significance and further evaluate its diagnostic value for NSCLC. Methods. The levels of Linc00152 were detected in NSCLC tissues and plasma samples by quantitative real-time PCR (qRT-PCR). Receiver operating characteristic (ROC) curves were depicted to evaluate the diagnostic value. Results. We found that Linc00152 levels were upregulated in both NSCLC tissues and plasma samples. Plasma Linc00152 levels were significantly lower in postoperative samples than in preoperative samples. Besides, high Linc00152 expression was significantly correlated with tumor size ( , ) and tumor stage ( , ). The ROC curves indicated that plasma Linc00152 has high diagnostic accuracy for NSCLC, and the area under curve (AUC) for NSCLC versus healthy was 0.816 (95% CI: 0.757–0.875). Moreover, we found that the combination of Linc00152 and CEA could provide a more powerful diagnosis efficiency than Linc00152 or CEA alone (AUC = 0.881, 95% CI: 0.836–0.926). Conclusions. Plasma Linc00152 could serve as a promising biomarker for diagnosing and monitoring NSCLC.

Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases.

Abstract: High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.

CD146 Promoter Polymorphism (rs3923594) Is Associated with Recurrence of Clear Cell Renal Cell Carcinoma in Chinese Population.

Abstract: Introduction. CD146 is a membrane signal receptor in tumor-induced angiogenesis. However, limited studies have focused on the CD146 promoter polymorphisms in clear cell renal cell carcinoma (ccRCC). Purpose. The purpose of this study was to investigate the association between polymorphisms located in the promoter region of the CD146 gene and characteristics of ccRCC in Chinese population. The association between the CD146 promoter polymorphisms and CD146 expression was also investigated in ccRCC. Materials and Methods. A total of 600 samples including 300 ccRCC patients and 300 healthy controls were collected for analysis of the CD146 promoter polymorphisms by direct sequence. The CD146 expressions were measured by qRT-PCR. Results. We had not found any significant differences in genotypic and allelic frequencies of CD146 promoter polymorphisms between ccRCC patients and controls. The rs3923594 was associated with stage and metastasis (300 cases) and recurrence (263 cases) of ccRCC in Chinese population. A significant association was also observed between the rs3923594 and CD146 expression (227 cases) in ccRCC. Conclusions. CD146 promoter polymorphisms were not associated with the risk of ccRCC in Chinese population. The rs3923594 was an independent predictor of recurrence in Chinese patients with localized ccRCC.

The Ratio of C-Reactive Protein/Albumin is a Novel Inflammatory Predictor of Overall Survival in Cisplatin-Based Treated Patients with Metastatic Nasopharyngeal Carcinoma.

Abstract: The C-reactive protein/albumin (CRP/Alb) ratio has been recently identified as a prognostic factor in various cancers, whereas its role remains unclear in metastatic nasopharyngeal carcinoma (NPC). The current study retrospectively analyzed 148 patients with metastatic NPC who underwent cisplatin-based chemotherapy and further evaluated the prognostic value of the CRP/Alb ratio and its association with clinical characteristics in these patients. The optimal cut-off value was 0.189 for the CRP/Alb ratio. The high CRP/Alb ratio was significantly associated with elevated NLR, platelet-to-lymphocyte ratio (PLR), and EBV-DNA levels and decreased haemoglobin level (all p < 0.05). The results of multivariate analysis showed that the CRP/Alb ratio was an independent prognostic factor of overall survival. Patients with a high CRP/Alb ratio (≥0.189) had a 1.867 times (p = 0.024, 95% CI = 1.085-3.210) greater risk of mortality compared with those with a low CRP/Alb ratio (<0.189). In addition, combining the CRP/Alb ratio with GPS could accurately discriminate the prognosis of our patients. Our results suggested that the CRP/Alb ratio is a feasible and inexpensive tool for predicting survival outcomes and is a valuable coadjutant for the GPS to further identify differences in survivals of patients with metastatic NPC.

MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.

Abstract: Background. The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression. Aims. To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients. Methods. miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients. Conclusions. All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.

Heat Shock Protein HSP27 Secretion by Ovarian Cancer Cells Is Linked to Intracellular Expression Levels, Occurs Independently of the Endoplasmic Reticulum Pathway and HSP27's Phosphorylation Status, and Is Mediated by Exosome Liberation.

Abstract: The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock. Intra- and extracellular HSP27 amounts were assessed by Western blotting and ELISA. Protein secretion was blocked by brefeldin A and the impact of the HSP27 phosphorylation status was analyzed overexpressing HSP27 phosphomutants. The present study demonstrated that HSP27 secretion by OVCAR-3 and SK-OV-3 cells depends on intracellular HSP27 concentrations. Moreover, HSP27 secretion is independent of the endoplasmic reticulum secretory pathway and HSP27 phosphorylation. Notably, analysis of OC cell-born exosomes not only confirmed the concentration-dependent correlation of HSP27 expression and secretion but also demonstrated a concentration-dependent incorporation of HSP27 protein into exosomes. Thus, secreted HSP27 may become more important as an extracellular factor which controls the tumor microenvironment and might be a noninvasive biomarker.