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Open Access journal
ISSN (Print) 0278-0240 - ISSN (Online) 1875-8630
Published by Hindawi [333 journals]
- Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and
Prognosis of Colorectal Cancer?
Abstract: Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies.
PubDate: Thu, 16 Mar 2017 00:00:00 +000
- Efficacy of Nucleot(s)ide Analogs Therapy in Patients with Unresectable
HBV-Related Hepatocellular Carcinoma: A Systematic Review and
Abstract: Aim. To determine whether nucleot(s)ide analogs therapy has survival benefit for patients with HBV-related HCC after unresectable treatment. Method. A systematic search was conducted through seven electronic databases including PubMed, OVID, EMBASE, Cochrane Databases, Elsevier, Wiley Online Library, and BMJ Best Practice. All studies comparing NA combined with unresectable treatment versus unresectable treatment alone were considered for inclusion. The primary outcome was the overall survival (OS) after unresectable treatment for patients with HBV-related HCC. The secondary outcome was the progression-free survival (PFS). Results were expressed as hazard ratio (HR) for survival with 95% confidence intervals. Results. We included six studies with 994 patients: 409 patients in nucleot(s)ide analogs therapy group and 585 patients without antiviral therapy in control group. There were significant improvements for the overall survival (HR = 0.57; 95% CI = 0.47–0.70; p < 0.001) and progression-free survival (HR = 0.84; 95% CI = 0.71–0.99; p = 0.034) in the NA-treated group compared with the control group. Funnel plot showed that there was no significant publication bias in these studies. When it comes to antiviral drugs and operation method, it also showed benefit in NA-treated group. At the same time, overall mortality as well as mortality secondary to liver failure in NA-treated group was obviously lesser. Sensitivity analyses confirmed the robustness of the results. Conclusions. Nucleot(s)ide analogs therapy after unresectable treatment has potential beneficial effects in terms of overall survival and progression-free survival. NA therapy should be considered in clinical practice.
PubDate: Wed, 15 Mar 2017 09:57:02 +000
- Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A
Abstract: Background. Previous studies have revealed that gene polymorphisms of inflammatory factors may influence the development or progression of periodontitis, a main cause of tooth loss in adults; however, due to limitations of individual studies, inconsistent findings were reported. Objective. To meta-analytically investigate the relationship between periodontitis and the Interleukin-4 (IL-4) and Interleukin-4 receptor (IL-4R) gene polymorphisms. Methods. Databases were searched for relevant case-control studies. After study selection based on the predefined selection criteria, methodological quality assessment and data extraction were conducted independently by two reviewers, before subsequent statistical analyses. Results. 37 studies involving 4,385 patients and 5,168 controls were included. All the studied IL-4 polymorphisms were not significantly associated with periodontitis, except the -33C/T (CT versus CC: OR = 0.50, 95% CI = 0.28–0.88) associated with reduced AgP susceptibility. Positive association was found between IL-4R Q551 polymorphism and periodontitis susceptibility in three genetic models (R versus Q: OR = 1.59, 95% CI = 1.14–2.22; QR versus QQ: OR = 1.84, 95% CI = 1.21–2.80; RR + QR versus QQ: OR = 1.82, 95% CI = 1.22–2.72). Conclusions. A positive association exists between the IL-4R Q551R polymorphism and occurrence of CP. The IL-4 -33 CT genotype is negatively associated with the occurrence of AgP.
PubDate: Tue, 14 Mar 2017 00:00:00 +000
- The Exploration of Peptide Biomarkers in Malignant Pleural Effusion of
Lung Cancer Using Matrix-Assisted Laser Desorption/Ionization
Time-of-Flight Mass Spectrometry
Abstract: Background. Diagnoses of malignant pleural effusion (MPE) are a crucial problem in clinics. In our study, we compared the peptide profiles of MPE and tuberculosis pleural effusion (TPE) to investigate the value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of MPE. Material and Methods. The 46 MPE and 32 TPE were randomly assigned to training set and validation set. Peptides were isolated by weak cation exchange magnetic beads and peaks in the range of 800–10000 Da were analyzed. Comparing the peptide profile between 30 MPE and 22 TPE samples in training set by ClinProTools software, we screened the specific biomarkers and established a MALDI-TOF-MS classification of MPE. Finally, the other 16 MPE and 10 TPE were included to verify the model. We additionally determined carcinoembryonic antigen (CEA) in MPE and TPE samples using electrochemiluminescent immunoassay method. Results. Five peptide peaks (917.37 Da, 4469.39 Da, 1466.5 Da, 4585.21 Da, and 3216.87 Da) were selected to separate MPE and TPE by MALDI-TOF-MS. The sensitivity, specificity, and accuracy of the classification were 93.75%, 100%, and 96.15%, respectively, after blinded test. The sensitivity of CEA was significantly lower than MALDI-TOF-MS classification (). Conclusions. The results indicate MALDI-TOF-MS is a potential method for diagnosing MPE.
PubDate: Mon, 13 Mar 2017 06:47:41 +000
- Genotyping of IL-4 −590 (C>T) Gene in Iraqi Asthma Patients
Abstract: This study is the first investigation in Iraq dealing with genotyping of IL-4 −590 (C>T) gene, especially in Iraqi patients with asthma. We studied forty-eight blood samples collected from patients with asthma and compared with age-matched 25 healthy individuals as controls. The polymorphism results of IL-4 −590 (C>T) gene by using amplification refractory mutation system (ARMS-PCR) showed the presence of C and T alleles and three genotypes (CC, CT, and TT). Interestingly the frequency of C allele and CC genotype was higher in patients with asthma in comparison with the same allele and genotype in control (P 1 × 10−6). This increase was associated with an increased risk factor of asthma (odds ratio [OR] 9.21; 95% confidence interval [CI] 3.58–23.71). Genotypes analysis by using Hardy-Weinberg distribution showed no significant differences between patients with asthma and healthy subjects. In conclusion, the increasing risk of asthma was associated with C allele and the CC genotype and these are revealed as etiological fraction with risk by having this disease, while the T allele percentage ratio in controls was higher when it is compared with asthma patients suggesting that these alleles have a protective effect (preventive fraction).
PubDate: Sun, 12 Mar 2017 08:10:16 +000
- Corrigendum to “Predictive Value of Plasma MicroRNA-216a/b in the
Diagnosis of Esophageal Squamous Cell Carcinoma”
PubDate: Sun, 12 Mar 2017 00:00:00 +000
- Association between VEGF Gene Polymorphisms and In-Stent Restenosis after
Coronary Intervention Treated with Bare Metal Stent
Abstract: Background. In-stent restenosis (ISR) is the gradual narrowing of the vessel lumen after coronary stent implantation due to the increase in vascular smooth muscle cell proliferation. Vascular endothelial growth factor (VEGF) protein plays an important role in this process. Our aim was to analyze the association of single nucleotide polymorphisms of the VEGF gene (rs2010963 and rs6999447) with the occurrence of ISR after coronary artery bare metal stent (BMS) implantation. Methods. 205 patients with a history of BMS implantation and a repeated coronarography were prospectively enrolled. Patients were assigned to diffuse restenosis group () and control group () and VEGF genotypes were determined. Results. Diffuse ISR was significantly more frequently observed in patients with homozygous normal genotype of rs2010963 polymorphism, and this polymorphism was independently associated with diffuse ISR. Conclusions. RS2010963 is associated with higher incidence of development of diffuse coronary ISR in patients treated with BMS implantation.
PubDate: Tue, 07 Mar 2017 07:00:05 +000
- Ischemia-Modified Albumin as a Marker of Acute Coronary Syndrome: The Case
for Revising the Concept of “N-Terminal Modification” to “Fatty Acid
Occupation” of Albumin
Abstract: Ischemia-modified albumin (IMA) is assumed “N-terminal modified” albumin which is generated immediately following myocardial ischemia. The diagnosis of IMA is based on reduced cobalt binding affinity to albumin which is attributed mainly to incapability of cobalt to bind at albumin’s modified N-terminus. Although the albumin cobalt binding test was accepted as a potentially powerful marker for discriminating acute coronary syndrome from nonischemic chest pain, its usefulness has been brought into question in recent years. Patients with acutely ischemic myocardium exhibit a rapid increase in serum levels of fatty acids (FAs). Almost all released FAs are strongly bound to albumin which create conformational changes in the protein with resultant reduced cobalt binding affinity. There is a clear metabolic and temporal relationship between IMA measured via albumin cobalt binding testing and serum levels of FAs. In line with what has been suggested recently in the literature, we conclude that a shift from the concept of “N-terminal modified” to “FA-occupied” albumin is required, as this better describes IMA in patients with acute coronary syndrome. We also offer “oxidation modified albumin, OMA,” which is conceptually different from the “FA-occupied” IMA, to describe modification of albumin in chronic disease associated with increased oxidative stress.
PubDate: Sun, 05 Mar 2017 10:02:18 +000
- A Panel of CA19-9, Ca125, and Ca15-3 as the Enhanced Test for the
Differential Diagnosis of the Pancreatic Lesion
Abstract: Background. Proper diagnosis of pancreatic lesion etiology is a challenging clinical dilemma. Studies suggest that surgery for suspected pancreatic ductal adenocarcinoma (PDAC) reveals a benign lesion in 5% to 13% of cases. The aim of our study was to assess whether routinely used biomarkers such as CA19-9, Ca125, Ca15-3, and CEA, when combined, can potentially yield an accurate test predicting pancreatic lesion etiology. Methods. We retrospectively analyzed data of 326 patients who underwent a diagnostic process due to pancreatic lesions of unknown etiology. Results. We found statistically significant differences in mean levels of all biomarkers. In logistic regression model, we applied levels CA19-9, Ca125, and Ca15-3 as variables. Two validation methods were used, namely, random data split into training and validation groups and bootstrapping. Afterward, we built ROC curve using the model that we had created, reaching AUC = 0,801. With an optimal cut-off point, it achieved specificity of 81,2% and sensitivity of 63,10%. Our proposed model has superior diagnostic accuracy to both CA19-9 ( = 0,0194) and CA125 ( = 0,0026). Conclusion. We propose a test that is superior to CA19-9 in a differential diagnosis of pancreatic lesion etiology. Although our test fails to reach exceptionally high accuracy, its feasibility and cost-effectiveness make it clinically useful.
PubDate: Sun, 05 Mar 2017 07:14:08 +000
- Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related
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.
PubDate: Wed, 01 Mar 2017 07:44:21 +000
- Hyperferritinemia as a Diagnostic Marker for Severe Fever with
Abstract: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all ). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS.
PubDate: Tue, 28 Feb 2017 00:00:00 +000
- A Novel Panel of Serum Biomarkers for MPM Diagnosis
Abstract: Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.
PubDate: Tue, 28 Feb 2017 00:00:00 +000
- Combined Genetic Biomarkers Confer Susceptibility to Risk of Urothelial
Bladder Carcinoma in a Saudi Population
Abstract: We evaluated the associations between seven single nucleotide polymorphisms and susceptibility to urothelial bladder carcinoma (UBC) in a Saudi population. Genomic DNA was taken from buccal cells of 52 patients with UBC and 104 controls for genotyping of GSTT1, GSTM1, rs4646903, rs1048943, TP53 rs1042522, rs1801133, and rs1801394 using PCR and TaqMan® assays. The rs1801133 and rs1801394 variants showed strong associations with UBC (OR = 2.3, ; OR = 2.6, , resp.). Homozygosity of Pro72 conferred a significant double risk in cases compared with controls (30.8% versus 15.4%), but the homozygote Arg/Arg had no effect on risk. Genotypic combinations of GSTM1/GSTT1, rs4646903/rs1048943, and rs1801133/rs1801394 exhibited significant linkage with the disease (, ; , ; and , , resp.). The GSTM1 and rs1042522Arg and rs1801394G variant alleles were more frequent in current smokers with UBC (52.4%, 52.5%, and 64.3%, resp.) than were the corresponding wild-types. Despite some variants having only a slight effect on UBC risk, the interaction effect of combined genetic biomarkers—or even the presence of one copy of a variant allele—is potentially much greater. Perhaps more studies regarding next-generation genetic sequencing and its utility can add to the risk of UBC.
PubDate: Mon, 27 Feb 2017 07:06:04 +000
- Validity of a New Kit Measuring Salivary Lactate Dehydrogenase Level for
Abstract: Aim. The aim of this study was to determine the usefulness of a new kit that can evaluate salivary lactate dehydrogenase (LD) level in real time for screening gingivitis. Materials and Methods. The study included 70 systemic healthy volunteers [29 males and 41 females; mean age ± SD: years]. Resting saliva was collected from each participant and LD level was evaluated in real time using the kit (a color-changing sheet with an integer scale ranging from 1 to 10). A dentist measured probing pocket depth, clinical attachment level, and the proportion of sites with bleeding on probing (% BOP) at six sites on all teeth. Gingivitis was diagnosed when the BOP value was ≥20%. Results. Salivary LD level was positively correlated with mean % BOP (odds ratio: 1.47, 95% confidence interval: 1.132–1.916, and ) in a logistic regression model. The sensitivity and specificity of the kit were 0.89 and 0.98, respectively, at a cut-off value of 8.0 for LD level. Conclusions. The new kit for measurement of salivary LD level may be a useful tool to screen for gingivitis in young adults, which contributes to early detection of future periodontitis.
PubDate: Sun, 26 Feb 2017 00:00:00 +000
- 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.
PubDate: Thu, 23 Feb 2017 09:58:43 +000
- 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
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.
PubDate: Thu, 23 Feb 2017 09:20:36 +000
- Detection of Circulating Tumour Cells in Urothelial Cancers and Clinical
Correlations: Comparison of Two Methods
Abstract: Circulating tumour cells (CTC) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer (BC) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect (AT) and ScreenCell®Cyto (SC) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic () and 47 metastatic (M+) BC patients, at baseline (T0) and during treatment (T1). At T0, CTC positivity rates by AT were higher in M+ compared to M0 cases (57.4% versus 25%, p = 0.041). EPCAM was detected in 75% of CTC-positive samples by AT, showing increasing expression levels from T0 to T1 (median (interquartile range, IQR): 0.18 (0.07–0.42) versus 0.84 (0.33–1.84), ) in M+ cases. Overall, CTC positivity by SC was around 80% regardless of clinical setting and time point of analysis, except for a lower occurrence at T1 in M0 cases. At T0, circulating tumour microemboli were more frequently (25% versus 8%) detected and more numerous in M+ compared to M0 patients. The approach used for CTC detection impacts the outcome of CTC studies. Further investigations are required to clarify the clinical validity of AT and SC in specific BC clinical contexts.
PubDate: Wed, 22 Feb 2017 06:16:06 +000
- Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant
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.
PubDate: Tue, 21 Feb 2017 00:00:00 +000
- Association of Circulating IGFBP1 Level with the Severity of Coronary
Artery Lesions in Patients with Unstable Angina
Abstract: Aims. Local IGFBP1 level was reported to affect the development of coronary artery plaque. This study investigated the association of circulating IGFBP1 level with the severity of coronary artery lesions in patients with unstable angina. Materials and Methods. In 112 consecutive patients with clinically diagnosed unstable angina, admitted from July 2014 to July 2015, we studied the correlations of circulating IGFBP1 and the severity of coronary artery disease (CAD). Results. All patients underwent scheduled coronary angiography, and 67 cases were diagnosed with critical and 45 with noncritical CAD. Of the 67 critical CAD patients, 41 (61.19%) presented with multivessel and 26 (38.81%) with single-vessel lesions. IGFBP1 levels were higher in patients with multivessel than those with single-vessel lesions. Moreover, the IGFBP1 level was positively correlated with the GRACE score. Among clinical variables, the IGFBP1 level was correlated with HDL-C. IGFBP1 alone (cutoff 20.86 ng/ml) demonstrated a sensitivity of 0.448 and specificity of 0.933 in predicting CAD. Combination of IGFBP1 and HDL-C had a sensitivity of 0.821 and specificity of 0.800 in predicting CAD. Conclusions. Circulating IGFBP1 level positively correlated with the severity of CAD. IGFBP1, when combined with HDL-C, might be useful in screening for high risk CAD patients.
PubDate: Mon, 20 Feb 2017 07:59:26 +000
- Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for
Abstract: Cerebrospinal fluid (CSF) cytology has low sensitivity for leptomeningeal metastasis (LM); thus, new markers are needed to improve the diagnostic accuracy of LM. We measured carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) in paired samples of CSF and serum from patients with LM and patients with nonmalignant neurological diseases (NMNDs) as controls. Receiver operating curve analysis was performed to assess their diagnostic accuracy for LM. In patients with NMNDs, CEA and CYFRA 21-1 levels in the CSF were significantly lower than the serum levels. In patients with LM, there was no significant difference between the CSF and serum CEA levels, whereas the CYFRA 21-1 levels were significantly higher in the CSF than the serum. CSF/serum quotients of CYFRA 21-1 were higher than those of CEA in patients with LM and patients with NMNDs. CSF CYFRA 21-1 and CSF/serum quotient of CYFRA 21-1 had high accuracy for differentiating LM from NMNDs that was similar to CSF CEA and CSF/serum quotient of CYFRA 21-1, whereas serum CYFRA 21-1 is of poor diagnostic value. Measurement of CSF CYFRA 21-1 should not be overlooked in patients with suspected LM, even if the serum CYFRA 21-1 level is within normal limits.
PubDate: Sun, 19 Feb 2017 00:00:00 +000
- 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.
PubDate: Sun, 19 Feb 2017 00:00:00 +000
- Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous
Abstract: Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.
PubDate: Thu, 16 Feb 2017 00:00:00 +000
- 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 () in this study. Screening of 754 unique microRNAs was performed in the discovery phase () using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A , and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A 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 in all histological types, where miR-1274A 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.
PubDate: Wed, 15 Feb 2017 00:00:00 +000
- 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.
PubDate: Tue, 14 Feb 2017 00:00:00 +000
- The Impact of tagSNPs in CXCL16 Gene on the Risk of Myocardial Infarction
in a Chinese Han Population
Abstract: CXCL16 has been demonstrated to be involved in the development of atherosclerosis and myocardial infarction (MI). Nonetheless, the role of the CXCL16 polymorphisms on MI pathogenesis is far to be elucidated. We herein genotyped four tagSNPs in CXCL16 gene (rs2304973, rs1050998, rs3744700, and rs8123) in 275 MI patients and 670 control subjects, aimed at probing into the impact of CXCL16 polymorphisms on individual susceptibility to MI. Multivariate logistic regression analysis showed that C allele (OR = 1.31, 95% CI = 1.03–1.66, and ) and CC genotype (OR = 1.84, 95% CI = 1.11–3.06, and ) of rs1050998 were associated with increased MI risk; and C allele (OR = 0.77, 95% CI = 0.60–0.98, and ) of rs8123 exhibited decreased MI risk, while the other two tagSNPs had no significant effect. Consistently, the haplotype rs2304973T-rs1050998C-rs3744700G-rs8123A containing the C allele of rs1050998 and A allele of rs8123 exhibited elevated MI risk (OR = 1.41, 95% CI = 1.02–1.96, and ). Further stratified analysis unveiled a more apparent association with MI risk among younger subjects (≤60 years old). Taken together, our results provided the first evidence that CXCL16 polymorphisms significantly impacted MI risk in Chinese subjects.
PubDate: Tue, 14 Feb 2017 00:00:00 +000
- Differential Site-Based Expression of Pentose Phosphate Pathway-Related
Proteins among Breast Cancer Metastases
Abstract: Purpose. We aimed to investigate the expression of pentose phosphate pathway- (PPP-) related proteins in metastatic breast cancer and its relationship with clinicopathologic factors. Methods. Tissue samples from 126 metastatic breast cancers were included in a tissue microarray. Expression of PPP-related proteins [glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), 6-phosphogluconate dehydrogenase (6PGDH), and nuclear factor erythroid 2-related factor (NRF2)] was determined by immunohistochemistry. Results. G6PDH () and cytoplasmic NRF2 () showed the highest expression in brain metastases. Human epidermal growth factor receptor (HER-2) positivity was associated with G6PDH () and cytoplasmic NRF2 () positivity. A high Ki-67 labeling index (LI) was correlated with nuclear NRF2 positivity (), and HER-2-positive luminal B type was associated with G6PDH positivity (). On multivariate Cox analysis, independent risk factors of short overall survival were 6PGL positivity in bone metastasis (HR 4.180, 95% CI 1.160–15.06, ) and low Ki-67 LI in lung metastasis (HR 11.853, 95% CI 1.841–76.30, ). Conclusion. Differential expression of PPP-related proteins correlated with different prognoses and metastatic sites, with the highest expression in brain metastases, and could be a potential therapeutic target.
PubDate: Thu, 02 Feb 2017 06:23:29 +000
- Elevated Concentrations of SERPINE2/Protease Nexin-1 and Secretory
Leukocyte Protease Inhibitor in the Serum of Patients with Papillary
Abstract: Introduction. SERPINE2 and secretory leukocyte protease inhibitor (SLPI) are proteins with anticoagulant properties which could promote solid tumor growth. However, their role in the pathogenesis of thyroid cancer has not been determined. Materials and Methods. The aim of this study was to assess serum SERPINE2 and SLPI concentrations in a group of 36 patients with papillary thyroid cancer (PTC) and a group of 19 subjects with multinodular nontoxic goiter (MNG). The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum SERPINE2 and SLPI concentrations were measured using specific ELISA methods. Results. Significantly higher concentrations of SERPINE2 and SLPI were found in patients with PTC as compared with MNG and controls. Positive correlation was found between SERPINE2 and SLPI concentrations in PTC patients. The levels of SERPINE2 and SLPI did not differ significantly between MNG and healthy controls. Conclusions. Our results indicate that SERPINE2 and SLPI play a significant role in the development of papillary thyroid cancer and imply that the evaluation of serum concentrations of both anticoagulant molecules may be considered as additional marker for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors.
PubDate: Tue, 31 Jan 2017 13:42:59 +000
- The Impact of the Expression Level of Intratumoral Dihydropyrimidine
Dehydrogenase on Chemotherapy Sensitivity and Survival of Patients in
Gastric Cancer: A Meta-Analysis
Abstract: The potential impact that the intratumoral expression level of dihydropyrimidine dehydrogenase (DPD) has on chemotherapy sensitivity and long-term survival for gastric cancer (GC) patients remains controversial; therefore, this study seeks to clarify this issue. Our meta-analysis was performed using Review Manager (RevMan) 5.3 software. In vitro drug sensitivity tests, correlation coefficients between sensitivity to 5-fluorouracil (5-FU), and expression levels of intratumoral DPD were used as effective indexes to analyse. Overall survival (OS) and progression-free survival (PFS) were used as endpoints for patient outcome, and hazard ratios (HRs) and 95% confidence intervals (CIs) were noted as measures of effect. There were 15 eligible studies including 1805 patients for the final analysis. The analysis revealed a statistically significant difference between the expression level of intratumoral DPD activity, DPD mRNA levels, and sensitivity to 5-FU in GC patients, with high expression levels of intratumoral DPD resulting in low sensitivity to 5-FU. However, no matter what therapeutic regimens were used, there was no significant difference for patient outcomes between high and low DPD expression groups, either in OS or in PFS. In conclusion, high levels of intratumoral DPD expression have a negative impact on sensitivity to 5-FU in GC patients, but no prognostic value for long-term survival was uncovered.
PubDate: Tue, 31 Jan 2017 10:05:44 +000
- Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in
Chinese Lung Transplant Patients
Abstract: Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/D ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated. Results. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus C/D ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus C/D ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus C/D ratios difference of IL-10 polymorphisms was found in our data. Conclusions. IL-18 polymorphisms may influence tacrolimus elimination in lung transplantation patients.
PubDate: Thu, 26 Jan 2017 14:28:52 +000
- A Case-Control Study of the Association between Polymorphisms in the
Fibrinogen Alpha Chain Gene and Schizophrenia
Abstract: Our previous studies using the mass spectrum analysis provided evidence that fibrinopeptide A (FPA) could be a potential biomarker for schizophrenia diagnosis. We sought further to demonstrate that variants in the fibrinogen alpha chain gene (FGA) coded FPA might confer vulnerability to schizophrenia. 1,145 patients with schizophrenia and 1,016 healthy volunteers from the Han population in Northeast China were recruited. The association of three tag single nucleotide polymorphisms (SNPs) (rs2070011 in the UTR, rs2070016 in intron 4, and rs2070022 in the UTR) in FGA and schizophrenia was examined using a case-control study design. Genotypic distributions of these three SNPs were not found to be significantly different between cases and controls (rs2070011: , ; rs2070016: , ; rs2070022: , ). There were also no significant differences in SNP allelic frequencies between cases and controls (all ). Additionally, the frequency of haplotypes consisting of alleles of these three SNPs was not significantly different between cases and healthy control subjects (global , ). Our study did not show a significant association of FGA SNPs with schizophrenia. Future studies may need to test more FGA SNPs in a larger sample to identify those SNPs with a minor or moderate effect on schizophrenia.
PubDate: Thu, 19 Jan 2017 00:00:00 +000