New Biomarkers For Early Diagnosis Research Articles

Biomarkers of connective tissue disease-associated interstitial lung disease in bronchoalveolar lavage fluid: A label-free mass spectrometry-based relative quantification study.

BackgroundThe pathogenesis of connective tissue disease‐associated interstitial lung disease (CTD‐ILD) is unclear. This study aims to identify differentially expressed proteins (DEPs) in CTD‐ILD to determine the potential role of these DEPs that may play in the pathogenesis of CTD‐ILD and to offer potential therapeutic targets.MethodsBronchoalveolar lavage fluid (BALF) samples were collected from four patients with CTD‐ILD and four patients without CTD‐ILD. Label‐free mass spectrometry‐based relative quantification was used to identify the DEPs. Bioinformatics were used to determine the potential biological processes and signaling pathways associated with these DEPs.ResultsWe found 65 upregulated DEPs including SFTPD, CADM1, ACSL4, TSTD1, CD163, LUM, SIGLEC1, CPB2, TGFBI and HGD, and 67 downregulated DEPs including SGSH, WIPF1, SIL1, RAB20, OAS3, GMPR2, PLBD1, DNAJC3, RNASET2 and OAS2. The results of GO functional annotation for the DEPs showed that the DEPS were mainly enriched in the binding, cellular anatomical entity, cellular processes, and biological regulation GO terms. The results of KEGG analyses showed that the pathways most annotated with the DEPs were complement and coagulation cascades, metabolic pathways, pathways in cancer, and PPAR signaling pathway. COG analyses further informed the functions associated with these DEPs, with most focused on signal transduction mechanisms; posttranslational modification, protein turnover, chaperones; intracellular trafficking, secretion, and vesicular transport; amino acid transport and metabolism; and lipid transport and metabolism.ConclusionsDEPs identified between patients with vs. without CTD‐ILD may play important roles in the development of CTD‐ILD and are potential new biomarkers for early diagnosis of CTD‐ILD.

Underestimated Prediabetic Biomarkers: Are We Blind to Their Strategy?

Type 2 Diabetes (T2D) is currently one of the fastest growing health challenging, a non-communicable disease result of the XXI century lifestyle. Given its growing incidence and prevalence, it became increasingly imperative to develop new technologies and implement new biomarkers for early diagnosis in order to promote lifestyle changes and thus cause a setback of the disease. Promising biomarkers have been identified as predictive of T2D development; however, none of them have yet been implemented in clinical practice routine. Moreover, many prediabetic biomarkers can also represent potential therapeutical targets in disease management. Previous studies have identified the most popular biomarkers, which are being thoroughly investigated. However, there are some biomarkers with promising preliminary results with limited associated studies; hence there is still much to be understood about its mechanisms and associations in T2D pathophysiology. This work identifies and discusses the promising results of Galectin-3, Ophthalmate and Fetuin-A.

Assets of Circulating Extracellular Vesicles for Early Diagnosis and Prognosis of Gastric Cancer by Liquid Biopsy

Gastric cancer (GC) is an important human cancer, which needs new biomarkers for early diagnosis in order to improve the patients outcome. The aim of this review is to stress the huge interest of extracellular vesicles circulating into blood and other body fluids, as potential candidates for early diagnosis of gastric cancer. After briefly recalling the previous blood-based liquid biopsies as a non-invasive help to GC diagnosis and the main properties of extracellular vesicles, the review will be focused on the recent progressive emergence of exosomes as important partners in GC liquid biopsy. Faced with the always increasing number of exosomal biomarker candidates, the necessity of two independent searches is suggested. The biologists need to solve some pending biological problems about extracellular vesicles, and the eukaryotic microorganism Dictyostelium discoideum might be an appealing both "in vitro and in vivo" model for that purpose. On the other hand, the protocols for isolation and characterization of extracellular vesicles and their cargoes have to be strictly standardized for a further validation at a large scale, prerequisite for an efficient clinical translation of some promising biomarker (s) for gastric cancer diagnosis and prognosis.

Differential expression of long non-coding RNAs as diagnostic markers for lung cancer and other malignant tumors.

Due to advances in chip and sequencing technology, several types and numbers of long non-coding RNAs (lncRNAs) have been identified. LncRNAs are defined as non-protein-coding RNA molecules longer than 200 nucleotides, and are now thought as a new frontier in the study of human malignant diseases including NSCLC. Diagnosis of numerous malignant tumors has been closely linked to the differential expression of certain lncRNAs. LncRNAs are involved in gene expression regulation at multiple levels of epigenetics, transcriptional regulation, and post-transcriptional regulation. Mutations, deletions, or abnormal expression levels lead to physiological abnormalities, disease occurrence and are closely associated with human tumor diseases. LncRNAs play a crucial role in cancerous processes as either oncogenes or tumor suppressor genes. The expression of lncRNAs can regulate tumor cell in the proliferation, migration, apoptosis, cycle, invasion, and metastasis. As such, lncRNAs are potential diagnostic and treatment targets for cancer. And that, tumor biomarkers need to be detectable in easily accessible body samples, should be characterized by high specificity and sufficient sensitivity. Herein, it is significant clinical importance to screen and supplement new biomarkers for early diagnosis of lung cancer. This study aimed at systematically describing lncRNAs from five aspects based on recent studies: concepts, classification, structure, molecular mechanism, signal pathway, as well as review lncRNA implications in malignant tumor.

Identification of Tumor Antigens in Ovarian Cancers Using Local and Circulating Tumor-Specific Antibodies.

Ovarian cancers include several disease subtypes and patients often present with advanced metastatic disease and a poor prognosis. New biomarkers for early diagnosis and targeted therapy are, therefore, urgently required. This study uses antibodies produced locally in tumor-draining lymph nodes (ASC probes) of individual ovarian cancer patients to screen two separate protein microarray platforms and identify cognate tumor antigens. The resulting antigen profiles were unique for each individual cancer patient and were used to generate a 50-antigen custom microarray. Serum from a separate cohort of ovarian cancer patients encompassing four disease subtypes was screened on the custom array and we identified 28.8% of all ovarian cancers, with a higher sensitivity for mucinous (50.0%) and serous (40.0%) subtypes. Combining local and circulating antibodies with high-density protein microarrays can identify novel, patient-specific tumor-associated antigens that may have diagnostic, prognostic or therapeutic uses in ovarian cancer.

Role of microRNA as a marker in detection of diabetic nephropathy in type-2 diabetic Egyptian patients

Background Diabetic kidney disease (DKD) represents the major cause of chronic kidney disease. New biomarkers for early diagnosis of DKD are of interest. Our objective is to elucidate the significance of microRNA-192 (miRNA-192) and neutrophil gelatinase-associated lipocalin (NGAL) as early predictors of diabetic nephropathy in comparison with albuminuria in type-2 diabetic patients. Patients and methods A number of 45 persons in three groups, group 1: 15 healthy persons with no diabetes mellitus (DM). Group 2: 15 patients diagnosed with type-2 diabetes mellitus (T2DM) without albuminuria. Group 3: 15 patients diagnosed with T2DM with albuminuria. Estimation of serum miRNA, NGAL, urine albumin/creatinine ratio, serum creatinine, urea, fasting blood glucose, 2-h postprandial blood glucose, and glycated hemoglobin. Results The study showed that the serum miRNA-192 and NGAL levels were significantly higher in patients diagnosed with T2DM with albuminuria in comparison with patients diagnosed with T2DM without albuminuria. There was a significant positive correlation between miRNA-192 and NGAL and urine albumin/creatinine ratio. Conclusion Serum NGAL and miRNA-192 may serve as tools to follow up the development and progression of DKD.

Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis.

BackgroundThe incidence of osteoarthritis (OA), a chronic degenerative disease, is increasing every year. There is no effective clinical treatment for OA and the pathological mechanism remains unclear. Early diagnosis is an effective strategy to control the progress of OA. In this study, we aimed to identify potential early diagnostic biomarkers.MethodsWe downloaded the gene expression profile dataset, GSE51588 and GSE55235, from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were screened out using the “limma” R package. Weighted gene co-expression network analysis (WGCNA) was utilized to build the co-expression network between the normal and OA samples. A Venn diagram was constructed to detect the hub genes. Potential molecular mechanisms and signaling pathways were enriched by gene set variation analysis (GSVA). Single sample gene set enrichment analysis (ssGSEA) was used to identify the immune infiltration of OA.ResultsWe screened out three hub genes based on WGCNA and DEGs in this study. GSVA results showed that nuclear factor interleukin-3 (NFIL3) was related to tumor necrosis factor alpha (TNF-α) signaling via nuclear factor kappa-B (NF-κB), the reactive oxygen species pathway, and myelocytomatosis (MYC) targets v2. Highly-expressed ADM (adrenomedullin) pathways included TNF-α signaling via NF-κB, the reactive oxygen species pathway, and ultraviolet (UV) response up. OGN (osteoglycin)-enriched pathways included epithelial mesenchymal transition, coagulation, and peroxisome.ConclusionsWe identified three hub genes (NFIL3, ADM, and OGN) that were correlated to the development and progression of OA, which may provide new biomarkers for early diagnosis.

A Functional Variant of CXCL16 Is Associated With Predisposition to Sepsis and MODS in Trauma Patients: Genetic Association Studies.

PurposeCXC chemokines are mediators which mediate immune cells migration to sites of inflammation and injury. Chemokine C-X-C motif ligand 16 (CXCL16) plays an important role in the occurrence and development of sepsis through leukocyte chemotaxis, leukocyte adhesion and endotoxin clearance. In this study, we selected a set of tagging single nucleotide polymorphisms (tag SNPs) in the CXCL16 gene and investigated their clinical relevance to the development of sepsis and multiple organ dysfunction syndrome (MODS) in patients with major trauma in three independent Chinese Han populations.MethodsA total of 1,620 major trauma patients were enrolled in this study. Among these patients, 920 came from Chongqing in western China, 350 came from Zhejiang Province in eastern China, and 350 came from Guizhou Province in southwestern China. The improved multiplex ligation detection reaction (iMLDR) method was employed in the genotyping and genetic association analyses to determine the associations between CXCL16 haplotypes and sepsis morbidity rate and higher MOD scores in three cohorts.ResultsOnly CXCL16 T123V181 haplotype was associated with an increased risk for sepsis morbidity and higher MOD scores in the three cohorts (OR = 1.89, P = 0.001 for the Chongqing cohort; OR = 1.76, P = 0.004 for the Zhejiang cohort; OR = 1.55, P = 0.012 for the Guizhou cohort). The effect of T123V181 haplotype on the chemotaxis, migration and endotoxin clearance of immune cells were further observed. Protein modeling analysis showed that T123 and V181 might alter the structure of the CXCL16 active center. Thus it enhanced the chemotaxis and adhesion ability of immunocytes.ConclusionWe demonstrate the mechanism of CXCL16 T123V181 haplotype which regulates the sepsis morbidity rate and thus provide a new biomarker for early diagnosis of sepsis and MODS.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT01713205 (https://www.clinicaltrials.gov/ct2/results?cond=&term=+NCT01713205&cntry=&state=&city=&dist=).

Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer’s disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595–2.474), total-tau (SMD = 1.224, 95% CI: 0.534–1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795–4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.

Systematic Metabolic Profiling of Mice with Dextran Sulfate Sodium-Induced Colitis.

PurposeInflammatory bowel diseases (IBD) are a chronic inflammatory disease, which affects almost all tissues in the body. Previous studies mainly focused on breathing, fecal, and urine samples of patients with IBD. However, there is no comprehensive metabolomic analysis of the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues. Therefore, the aim of our study is to evaluate the utility metabolomic analysis of target tissues in the pathogenesis of IBD in exploring new biomarkers for early diagnosis and treatment.MethodsMale Sprague–Dawley rats were randomly allocated to control and DSS-treated groups (n = 7). Dextran sulfate sodium (DSS) was orally administered for 6 weeks. Gas chromatography-mass spectrometry (GC-MS) was used for metabolite determination, multivariate statistical analysis was used to identify metabolites that were differentially expressed in two groups.ResultsOur results showed that 3, 11, 12, 6, 5, 13, 13, and 11 metabolites were differentially expressed between the DSS treatment group and the control group in the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues, respectively. The most significant change of metabolites in the study was amino acid (L-alanine, L-glutamic acid, L-phenylalanine, L-proline, L-lysine, L-isoleucine, L-tryptophan, L-norleucine, L-valine, glycine, serine, L-threonine), organic acid (citric acid, 3-hydroxybutyric acid, propanoic acid), glucide (D-arabinose, D-fructose) and purine (9H-purin-6-ol, D-ribose) profiles. Several pathways were affected according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as alanine, aspartate, and glutamate metabolism, glutathione metabolism) to purine metabolism (aminoacyl-tRNA biosynthesis).ConclusionUsing GC-MS-based profiling of metabolite changes, these results may provide a more comprehensive view for IBD and IBD-related diseases and improve the understanding of IBD pathogenesis.

Circulating serum exosomal miR-92a-3p as a novel biomarker for early diagnosis of gastric cancer.

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal miR-92a-3p could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal miR-92a-3p in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal miR-92a-3p in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curvefor serum exosomal miR-92a-3p was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal miR-92a-3p, CEA and CA19-9 wasmore sensitive than anyof the three alone or any pair.These results showed that serum exosomal miR-92a-3p could be used as a novel new tumor biomarker to improve diagnostic efficiency inGC.

Alzheimer's polygenic risk score in general population reveals new biomarkers for early diagnosis

AbstractBackgroundIn aging population, Alzheimer's disease (AD) with its different stages (preclinical, prodromal, mild to severe) has a strong genetic component. For a given individual and using summary statistics available from powerful reference GWAS in Alzheimer’s disease (IGAP, Lambert, 2013), one can compute a Polygenic Risk Score (PRS) for AD, that is a cumulative genetic risk computed with one subject’s genome variants. Using individual's PRS and MRI images in an aging general population like UK Biobank, we could point at imaging markers (endophenotypes) associated with early stages of AD.Method16,549 subjects aged 47‐74 from UK Biobank were included in the analysis. Using anatomical T1 MRI images (3T), opening measurements in 123 sulci were extracted with BrainVisa/Morphologist pipeline. Individual's PRS were computed using PRSice and summary statistics from IGAP study and then have been tested for an association with sulcal opening measurements.ResultWe obtained 24 sulci for which opening measurements was either positively or negatively associated with PRS (p &lt; 0.05 after FDR correction). 17 sulcal opening showed increased widening w.r.t PRS with a main focus around the precuneus region, with superior parietal and central sulci. 7 sulcal opening showed opposite effect w.r.t the PRS and are located mostly in the orbital and insula region. See Figure for details.ConclusionFor neurological disease like AD that have a strong genetic background, the combination of genetics and imaging data in large, aging general population studies like UK Biobank, provides powerful tools to identify new possible early markers of neurodegeneration. Focus on early risk patterns as the ones presented here with a main result on parietal sulcal alterations might facilitate identification of individuals at risk for cognitive decline and possibly support diagnostic procedures for AD.

Detection of cognitive decline in metabolic syndrome

Abstract Background Metabolic syndrome (MetS), a risk factor for many vascular conditions, may be a prodromal manifestation of vascular cognitive impairment. Diagnosing early stages of cerebrovascular pathology can lead to prevention and delay of the progression of pathological conditions such as vascular cognitive impairment. Methods The objective of the study was to investigate new biomarkers for early diagnosis of MetS and cognitive decline as a follow-up. A cardiological, neuropsychological and neurological study was conducted among 75 Bulgarian participants. Beta amyloid in the blood, procalcitonin (PCT), NT-proBNP as predictors of cognitive impairment in patients with metabolic syndrome were identified. Clinical, anthropometric, biochemical, neuropsychological, cognitive and statistical data processing. Plasma amyloid beta (Aβ) levels, procalcitonin, NT-proBNP in MetS were investigated in participants with MetS and in group of healthy people. Results In the present study, plasma levels of Aβ42 and Aβ40 were found to be reduced in MetS participants. Procalcitonin concentration was significantly higher in males than in females. NT-proBNP was significantly higher in females than in males (p &amp;lt; 0.001). Regression analysis showed a positive relationship between NT-proBNP and systolic blood pressure (p &amp;lt; 0.001) and fasting blood glucose (p &amp;lt; 0.05). An inverse relation between NT-proBNP and diastolic blood pressure, waist circumference, triglycerides, HDL- and LDL cholesterol was found. Conclusions There was a positive association between PCT levels, decreased levels of Aβ42 and Aβ40, as well as elevated NT-proBNP and cognitive impairment in people with MetC. A concentration of NT-proBNP of 60 pg / ml or greater could be an indicator of metabolic abnormalities and early cognitive decline. Key messages Metabolic syndrome may be a prodromal manifestation of vascular cognitive impairment. The use of new biomarkers for diagnosis can lead to preventing and slowing the progression of complications associated with MetS.

MiRNA expression profile changes in the peripheral blood of monozygotic discordant twins for epithelial ovarian carcinoma: potential new biomarkers for early diagnosis and prognosis of ovarian carcinoma

BackgroundOvarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs.MethodsThe study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms.ResultsAfter the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant.ConclusionsThe detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data.There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.

Metabolomics profile in gastrointestinal cancers: Update and future perspectives.

Despite recent progress in diagnosis and therapy, gastrointestinal (GI) cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis. Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers; however, these tests are not useful as diagnostic screening since they have low specificity and low sensitivity. Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems, is now clear that this -omics could open a new way to study cancer. In the last years, nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for diseases' diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers. For these reasons in this review, we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.

Golgi Protein 73 versus Alpha-Fetoprotein as a New Biomarker in Early Diagnosis of Hepatocellular Carcinoma.

BackgroundScreening of early hepatocellular carcinoma (HCC) diagnosis is the greatest challenge for hepatologists. Alpha-fetoprotein (AFP) is the most common non-invasive biomarker used in HCC diagnosis.Objectives and AimsTo make a comparison between the new biomarker Golgi protein 73 (GP73) versus the standard biomarker AFP in the diagnosis of HCC.MethodsOur study was a case–control study, and 60 patients were included in the study. They were divided into two groups: 1) HCC patients with either chronic HBV or HCV infection (n=30); and 2) non-HCC patients with HBV or HCV infection who had either chronic hepatitis or liver cirrhosis (n=30). In addition, 30 healthy volunteers were included as a control group. Patients were subjected to liver function tests, kidney function tests, serum Golgi protein 73 and AFP levels. Imaging diagnosis of HCC was done by computed tomography (CT) or magnetic resonance imaging (MRI) based on American Association for the Study of Liver Diseases (AASLD) practice guidelines.ResultsStatistically significant differences between groups in terms of serum AFP (p<0.001) and GP73 (p<0.001) were found. Non-HCC patients (chronic hepatitis and liver cirrhosis) and HCC patients had significantly higher AFP and GP73 than the control group. In addition, patients with HCC had significantly higher AFP and GP73 than chronic hepatitis and cirrhotic patients. GP73 had higher diagnostic performance than AFP. At a cut-off value of ≥8.4 ng/mL, GP73 yielded a sensitivity of 86.7% and specificity of 89% for the discrimination between HCC and normal populations. Similarly, at a cut-off value of ≥8.45 ng/mL, GP73 yielded a sensitivity of 83.3% and specificity of 84% for the discrimination between HCC patients and non-HCC patients. On the other hand, AFP at a cut-off value of ≥2.4 ng/mL yielded a sensitivity of 75.4% and specificity of 90% for the discrimination between HCC and normal populations; and at a cut-off value of ≥20.85 ng/mL, AFP yielded a sensitivity of 72.2% and specificity of 86.2% for the discrimination between HCC and non-HCC patients.ConclusionGolgi protein 73 is a promising and accurate biomarker for early detection of HCC.

The relationship between insulin resistance, obesity, and endotrophin

Endotrophin is the cleavage product COL6. Recent findings indicate that endotrophin is actively involved in inflammation, angiogenesis, and fibrosis. It also seems to play a critical role in obesity-induced systemic insulin resistance by increasing chronic inflammation and fibrosis in adipose tissues. In this study, we aimed to reveal the relationship between human adipose tissue, inflammation, and insulin resistance (IR). The study included 51 IR patients and 37 healthy controls. The presence of IR was based on Homeostatic model of assessment-insulin resistance (HOMA-IR) level of 2, 7, or higher. Fasting plasma samples were obtained from the patients and the control group. The IR patients had a higher HOMA-IR, waist circumference, fasting plasma glucose (FPG), fasting insulin (FI), and triglyceride levels than the control subjects (p < 0.05). Endotrophin and CRP levels were significantly higher in patients with IR than controls (23.12 ± 18.32 ng/mL; 11.20 ± 6.60 ng/mL p < 0,001; 5.5 ± 3.37 ng/L; 1.97 ± 0.89 ng/L p < 0.001). The serum endotrophin level showed a positive correlation with HOMA-IR (r = 0.359; p < 0.001), waist circumference (r = 0.214; p < 0.05), FI (r = 0.386; p < 0.001), and CRP level (r = 0.251; p < 0.05) The serum endotrophin level was higher in patients with IR, independently of BMI, fasting glucose, and all other factors. Therefore, we foresee that high levels of endotrophin may be a new biomarker for early diagnosis of metabolic worsening in overweight and obesity. We also found a positive correlation between endotrophin and CRP. This indicates that endotrophin is closely related to inflammatory processes.

Combining Bioinformatics and Experiments to Identify and Verify Key Genes with Prognostic Values in Endometrial Carcinoma.

Endometrial carcinoma(EC) is the most common cancer of female reproductive system, thus requiring for new effective biomarkers which could predict the onset of EC and poor prognosis. Our study integrated two GEO datasets(i.e.GSE63678, GSE17025) and TCGA(The Cancer Genome Atlas ) UCEC data to screen out 344 common differentially expressed genes(DEGs), which were further analyzed by GO(gene ontology) functions and KEGG(Kyoto Encyclopedia of Gene and Genome) pathways. KEGG analysis results showed these DEGs were mainly enriched in cell cycle, oocyte meiosis, cellular senescence, carbon metabolism and p53 signaling pathway. Top 20 hub genes with higher degree were selected from PPI(protein-protein interaction) network and 15 of them were associated with the prognosis of EC, that is, CCNB2, CDC20, BUB1B, UBE2C, AURKB, FOXM1, NCAPG, RRM2, TPX2, DLGAP5, CDCA8, CDC45, MKI67, BUB1, KIF2C. UBE2C(Ubiquitin Conjugating Enzyme E2 C) was chosen for further validation in TCGA cohort on mRNA level and in our patient samples on protein level by immunohistochemistry. UBE2C was significantly highly expressed in endometrial carcinoma, and its expression level was associated with advanced FIGO staging and poor prognosis. Cox risk model demonstrated high UBE2C expression was an independent risk factor. Somatic mutations, elevated copy number, DNA hypomethylation all contributed to its overexpression. Therefore, by combination of bioinformatics and experiment, our study provided a unique insight into the pathogenesis and molecular mechanisms underlying EC and discovered new biomarkers for early diagnosis and prognostic prediction. UBE2C could serve as a potential marker to predict poor prognosis and as a therapeutic target.

KLHL14, an ovarian and endometrial-specific gene, is over-expressed in ovarian and endometrial cancer.

Ovarian cancer (OC) and endometrial cancer (EC) are two types of the most frequent gynecological malignancies worldwide. However, the prognosis of OC and EC patients remained gloomy. Therefore, there was still an urgent need to identify new biomarkers for early diagnosis and treatment of OC and EC. TCGA datasets were used to screen the KLHL14 expression levels in 18 different types of human cancers. TCGA datasets were also used to analyze the association between KLHL14 expression levels and OS/PFS in OC and EC. Human Protein Atlas was used to detected the KLHL14 protein levels in OC and EC. Kaplan-Meier plotter was used to evaluate the prognostic values of KLHL14 in Ovarian cancer. MAS 3.0 was used to perform GO and KEGG pathway analysis. STRING was used to perform PPI network. KLHL14 was specially expressed in OC and EC samples. Moreover, KLHL14 was found to be up-regulated in all stage of OC and EC samples. By analyzing Kaplan-Meier plotter and TCGA datasets, we found higher KLHL14 expression level was associated with shorter overall and progression-free survival in both OC and EC patients. Furthermore, GO and KEGG analysis of KLHL14 co-expressing genes indicated it played important roles in OC and EC progression. We for the first time reported KLHL14 was specially over-expressed in ovarian and endometrial cancer, up-regulation of KLHL14 was positively associated with worse outcome. Finally, we found knockdown of KLHL14 suppressed OC cell proliferation. KLHL14 could be a potential biomarker and therapy target for OC and EC.

Biobanking for discovery of novel cardiovascular biomarkers using imaging-quantified disease burden: protocol for the longitudinal, prospective, BioHEART-CT cohort study

IntroductionCoronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification and treatment of traditional risk factors. Data emerging over the past decade show...