scholarly journals Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chengjian Zhang ◽  
Shengnan Zhou ◽  
Huijing Chang ◽  
Feng Zhuang ◽  
Yang Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metabolic Pathways ◽  
Roc Curves ◽  
Serum Levels ◽  
Serum Biomarkers ◽  
Healthy Controls ◽  
Dodecylbenzenesulfonic Acid ◽  
Metabolomic Profiling ◽  
Liquid Chromatography Tandem Mass ◽  
Healthy Control

Background. The screening and early detection of colorectal cancer (CRC) still remain a challenge due to the lack of reliable and effective serum biomarkers. Thus, this study is aimed at identifying serum biomarkers of CRC that could be used to distinguish CRC from healthy controls. Methods. A prospective 1 : 2 individual matching case-control study was performed which included 50 healthy control subjects and 98 CRC patients. Untargeted metabolomic profiling was conducted with liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify CRC-related metabolites and metabolic pathways. Results. In total, 178 metabolites were detected, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish CRC patients from healthy controls. Nine metabolites showed significantly differential serum levels in CRC patients under the conditions of variable importance in projection VIP > 1 , p < 0.05 using Student’s t -test, and fold change FC ≥ 1.2 or ≤0.5. The above nine metabolites were 3-hydroxybutyric acid, hexadecanedioic acid, succinic acid semialdehyde, 4-dodecylbenzenesulfonic acid, prostaglandin B2, 2-pyrocatechuic acid, xanthoxylin, 12-hydroxydodecanoic acid, and formylanthranilic acid. Four potential biomarkers were identified to diagnose CRC through ROC curves: hexadecanedioic acid, 4-dodecylbenzenesulfonic acid, 2-pyrocatechuic acid, and formylanthranilic acid. All AUC values of these four serum biomarkers were above 0.70. In addition, the exploratory analysis of metabolic pathways revealed the activated states for the vitamin B metabolic pathway and the alanine, aspartate, and glutamate metabolic pathways associated with CRC. Conclusion. The 4 identified potential metabolic biomarkers could discriminate CRC patients from healthy controls, and the 2 metabolic pathways may be activated in the CRC tissues.

scholarly journals Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junchao Huang ◽  
Jinghui Tong ◽  
Ping Zhang ◽  
Yanfang Zhou ◽  
Yimin Cui ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Impairment ◽  
Cortical Thickness ◽  
Serum Levels ◽  
Healthy Controls ◽  
Tryptophan Pathway ◽  
Liquid Chromatography Tandem Mass ◽  
Therapeutic Development ◽  
Tryptophan Metabolites ◽  
Insight Into

AbstractA number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = −2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10−4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.

scholarly journals Shortened platelet half-life in multiple myeloma

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 514-520
Author(s):  
E Fritz ◽  
H Ludwig ◽  
W Scheithauer ◽  
H Sinzinger
Keyword(s):  
Multiple Myeloma ◽  
Half Life ◽  
Serum Levels ◽  
Statistical Correlation ◽  
Control Group ◽  
Healthy Controls ◽  
Platelet Factor ◽  
Healthy Control

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

scholarly journals Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

2020 ◽  
Vol 20 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Youn I Choi ◽  
Jun-Won Chung ◽  
Dong Kyun Park ◽  
Kyoung Oh Kim ◽  
Kwang An Kwon ◽  
...  
Keyword(s):  
Pilot Study ◽  
Medical History ◽  
Proton Pump ◽  
Serum Levels ◽  
Self Report ◽  
Healthy Controls ◽  
Control Subjects ◽  
Increased Risk ◽  
Healthy Control

Background/Aims: Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear.Materials and Methods: This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine.Results: Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (<i>P</i><0.005), 2.5 and 1.8 (<i>P</i><0.005), and 9.3 and 5.0 (<i>P</i><0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (<i>P</i><0.001), 2.0 (<i>P</i>=0.001), and 1.3 (<i>P</i>=0.3), respectively.Conclusions: Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.

scholarly journals Serum Levels of BDNF in Patients with Adenoma and Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Zhe Wang ◽  
Shuang Wang ◽  
Yu Liu ◽  
Shan Gao ◽  
Yunqing Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Diagnostic Performance ◽  
Serum Levels ◽  
Tnm Staging ◽  
Laboratory Method ◽  
Healthy Controls ◽  
Tumor Differentiation ◽  
Combined Detection ◽  
Control Study ◽  
Serum Bdnf

The present study is aimed at examining the serum levels of brain-derived neurotrophic factor (BDNF) and investigating its role in differential diagnosis of colorectal cancer (CRC). Materials and Methods. In a Chinese population, we conducted a case-control study to compare the diagnostic performance of serum levels of BDNF and carcinoembryonic antigen (CEA) for CRC. We enrolled 61 healthy controls, 31 patients with adenomas, and 81 patients with CRC. We explored the correlation between serum levels of BDNF and several pathological features, such as tumor differentiation and TNM staging. Results. The serum levels of BDNF were significantly ( p < 0.0001 ) higher in patients with CRC ( 10.64 ± 3.84 , n = 81 ) than in the healthy controls ( 4.69 ± 1.69   ng / mL , n = 61 ). Serum BDNF also correlated with tumor size, tumor differentiation, and TNM staging ( p < 0.05 ). For early diagnosis, the combination of BDNF (AUC 0.719; 95% CI, 0.621–0.816) and CEA (AUC 0.733; 95% CI, 0.632–0.909) slightly improved the diagnostic performance for CRC (AUC 0.823; 95% CI, 0.737-0.909). Conclusions. Combined detection of serum BDNF and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis of CRC.

scholarly journals Extracellular Vesicle-Based Detection of Pancreatic Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yesim Verel-Yilmaz ◽  
Juan Pablo Fernández ◽  
Agnes Schäfer ◽  
Sheila Nevermann ◽  
Lena Cook ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Roc Curves ◽  
Serum Levels ◽  
Extracellular Vesicle ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Healthy Controls ◽  
Precursor Lesions ◽  
Healthy Individuals ◽  
Serum Samples

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.

scholarly journals Reduced serum levels of pro-inflammatory chemokines in Fragile X Syndrome

2020 ◽  
Author(s):  
Anke Van Dijck ◽  
Susana Barbosa ◽  
Patricia Bermudez-Martin ◽  
Olfa Khalfallah ◽  
Cyprien Gilet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Robust Regression ◽  
Fragile X ◽  
Serum Levels ◽  
Unsupervised Clustering ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Clustering Method ◽  
Inflammatory Chemokines ◽  
Healthy Control

Abstract Background: Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological consequences of FXS are not solely confined to the central nervous system (CNS) but rather extend to other physiological dysfunctions in peripheral organs. To gain insights into possible immune dysfunctions in FXS, we profiled a large panel of immune-related biomarkers in the serum of FXS patients and healthy controls. Methods: We have used a sensitive and robust Electro Chemi Luminescence (ECL)-based immunoassay to measure the levels of 52 cytokines in the serum of n=25 FXS patients and n=29 healthy controls. We then used univariate statistics and multivariate analysis, as well as an advanced unsupervised clustering method, to identify combinations of immune-related biomarkers that could discriminate FXS patients from healthy individuals. Results: While the majority of the tested cytokines were present at similar levels in FXS patients and healthy individuals, nine chemokines, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26 and CXCL10, were present at much lower levels in FXS patients. Using robust regression, we show that six of these biomarkers (CCL2, CCL3, CCL11, CCL22, CCL26 and CXCL10) were negatively associated with FXS diagnosis. Finally, applying the K-sparse unsupervised clustering method to the biomarker dataset allowed for the identification of two subsets of individuals, which essentially matched the FXS and healthy control categories. Conclusions: Our data show that FXS patients exhibit reduced serum levels of several chemokines. This paves the way for further study of immune phenotypes in FXS patients.

scholarly journals Insulin Resistance and Oxidative Stress: In Relation to Cognitive Function and Psychopathology in Drug-Naïve, First-Episode Drug-Free Schizophrenia

2020 ◽  
Vol 11 ◽  
Author(s):  
Qi Tao ◽  
Yu Miao ◽  
Huihui Li ◽  
Xiuxia Yuan ◽  
Xufeng Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cognitive Function ◽  
Serum Levels ◽  
First Episode ◽  
Healthy Controls ◽  
Healthy Control ◽  
Drug Naïve ◽  
Drug Free ◽  
And Oxidative Stress

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients.Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied.Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P &lt; 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P &lt; 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = −0.345,−0.369,−0.444, respectively, P &lt; 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = −0.316 to −0.553, P &lt; 0.05).Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naïve, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients.

scholarly journals Circular RNA Expression Profiles in Plasma from Patients with Heart Failure Related to Platelet Activity

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 187 ◽  
Author(s):  
Yeying Sun ◽  
Xiaoli Jiang ◽  
Yan Lv ◽  
Xinyue Liang ◽  
Bingrui Zhao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Expression Profiles ◽  
Roc Curves ◽  
Serum Levels ◽  
Circular Rna ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Platelet Activity ◽  
Pathway Analyses

Heart failure (HF) is a deadly disease that is difficult to accurately diagnose. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that might play important roles in many cardiovascular diseases. However, their role in HF remains unclear. CircRNA microarrays were performed on plasma samples obtained from three patients with HF and three healthy controls. The profiling results were validated by quantitative reverse transcription polymerase chain reaction. The diagnostic value of circRNAs for HF was evaluated by receiver operating characteristic (ROC) curves. The expression profiles indicated that 477 circRNAs were upregulated and 219 were downregulated in the plasma of patients with HF compared with healthy controls. Among the dysregulated circRNAs, hsa_circ_0112085 (p = 0.0032), hsa_circ_0062960 (p = 0.0006), hsa_circ_0053919 (p = 0.0074) and hsa_circ_0014010 (p = 0.025) showed significantly higher expression in patients with HF compared with healthy controls. The area under the ROC curve for hsa_circ_0062960 for HF diagnosis was 0.838 (p < 0.0001). Correlation analysis showed that the expression of hsa_circ_0062960 was highly correlated with B-type natriuretic peptide (BNP) serum levels. Some differential circRNAs were found to be related to platelet activity by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The landscape of circRNA expression profiles may play a role in HF pathogenesis and improve our understanding of platelet function in HF. Moreover, hsa_circ_0062960 has potential as a novel diagnostic biomarker for HF.

Effect of oxaliplatin-capecitabine first-line chemotherapy and tumor response on serum proteomic profiles in advanced colorectal cancer and identification of diagnostic biomarkers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3603-3603
Author(s):  
H. H. Helgason ◽  
J. Y. Engwegen ◽  
A. Cats ◽  
H. Boot ◽  
H. G. Bonfrer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Number ◽  
Healthy Controls ◽  
First Line ◽  
Diagnostic Biomarkers ◽  
Standardized Protocol ◽  
Apolipoprotein A ◽  
Potential Biomarker ◽  
Healthy Control

3603 Background: Colorectal cancer (CRC) is the third most common cause of cancer related death. Prognosis is highly dependent on stage at diagnosis making early diagnosis mandatory. Previously we identified serum biomarkers for CRC, by comparing serum from CRC patients and healthy controls, using SELDI-TOF mass spectrometry. Methods: We validated our identified biomarkers and assessed the effect of first-line oxaliplatin (130 mg/m2 day 1, q21)-capecitabine (1000 mg/m2 d1–14, q21) therapy by prospective standardized serum sampling at < 2 weeks prior to start of chemotherapy and serially before each chemotherapy cycle in patients with advanced CRC. Samples were drawn according to standardized protocol, centrifuged within 1 hour and stored at -30°C. After thawing they were analyzed with SELDI-TOF MS on CM10 chips at pH 5. Healthy control subjects were matched according to age, gender and time of serum collection. For serial analysis the time points T: 0, 6, 12 and 18 - 24 weeks were used. All patients had given written consent, had WHO PS ≤ 2 and measurable disease, according to RECIST criteria, and/or were evaluable by CEA. Results: In total 42 patients (mean age: 57 years; range: 37 - 73; male 62%), were treated between 06/2003 and 09/2005. All patients were previously untreated except 8 patients who had received radiation or chemo-radiation for rectal carcinoma (all > 6 months). Median follow up was 45 weeks and median number of courses was 5.5 (range: 1 -10). Response rate was 46%; PR in 19, SD in 12 and PD in 10 patients, respectively (1 not evaluable) and median overall survival was 10.5 months. We identified 6 peptides/proteins (m/z: 31948, 8078, 28101 (apolipoprotein A-I), 7970, 5912 and 12861 Da, respectively (in order of significance) discriminating between CRC and healthy controls (p < 0.001). In a serial analysis of the patients a peptide, with m/z: 5.9-kDa (most likely fibrinogen split product) declined, during chemotherapy in some responsive patients, but apolipoprotein A-I appeared not to change. Conclusions: We confirmed our previous identification of apolipoprotein A-I (m/z: 28-kDa) as a potential biomarker for CRC and suggest a peptide with m/z: 5.9-kDa as a potential biomarker of response. No significant financial relationships to disclose.

Cytokine levels in patients (pts) with colorectal cancer and breast cancer and their relationship to fatigue and cognitive function

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9070-9070 ◽  
Author(s):  
J. L. Vardy ◽  
C. Booth ◽  
G. R. Pond ◽  
H. Zhang ◽  
J. Galica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Cognitive Function ◽  
Healthy Volunteers ◽  
Cognitive Dysfunction ◽  
Serum Levels ◽  
Healthy Controls ◽  
Post Surgery ◽  
Cytokine Levels ◽  
Perceived Cognitive Function

9070 Background: Cytokines have been associated with fatigue and cognitive dysfunction. Here we evaluated plasma cytokine levels in pts with colorectal cancer (CRC) and breast cancer (BC) who were free of evident disease, and in healthy volunteers. Methods: Serum levels of 10 cytokines were measured using a LiquiChip assay on 251 subjects. CRC pts (n=136, ages 23–75) were evaluated at baseline (mean 8 weeks post-surgery [n=107] or before surgery [n=29]), with repeat measures at 6 months (56 post chemotherapy [CT], 14 without CT) and 12 months (32 post CT, 7 without CT). BC pts (n=51, ages 29–60) were within 5 years of diagnosis (33 after adjuvant CT). Healthy volunteers (n=64) had ages 20–62. Cancer pts completed questionnaires for fatigue & QOL (FACT-F), anxiety/depression (GHQ), and perceived cognitive function (FACT-COG); they had neuropsychological assessment. Results: Cytokines were elevated in all cancer groups compared to healthy controls (p-values <0.001; selected data in table ). Values were highest after surgery but remained significantly higher than healthy controls at 6–60 months after diagnosis, with a trend to being higher in cancer patients who had not received CT. There was a trend to elevated cytokines being associated with greater fatigue and cognitive impairment in both CRC and BC, but no association with QOL or anxiety & depression. Conclusions: Cytokine levels were elevated in all cancer groups compared to healthy volunteers and remained elevated up to 5 years post diagnosis; they may be associated with cognitive dysfunction and fatigue. [Table: see text] No significant financial relationships to disclose.

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