BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.09.001
Gay Carter , Branko Miladinovic , Achintya A. Patel , Lauren Deland , Stephen Mastorides , Niketa A. Patel
{"title":"Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus","authors":"Gay Carter , Branko Miladinovic , Achintya A. Patel , Lauren Deland , Stephen Mastorides , Niketa A. Patel","doi":"10.1016/j.bbacli.2015.09.001","DOIUrl":"10.1016/j.bbacli.2015.09.001","url":null,"abstract":"<div><h3>Background</h3><p>Diabetes mellitus (DM), a metabolic disease, is characterized by impaired fasting glucose levels. Type 2 DM is adult onset diabetes. Long non-coding RNAs (lncRNAs) regulate gene expression and multiple studies have linked lncRNAs to human diseases.</p></div><div><h3>Methods</h3><p>Serum samples obtained from 96 participating veterans at JAH VA were deposited in the Research Biospecimen Repository. We used a two-stage strategy to identify an lncRNA whose levels correlated with T2DM. Initially we screened five serum samples from diabetic and non-diabetic individuals using lncRNA arrays. Next, GAS5 lncRNA levels were analyzed in 96 serum samples using quantitative PCR. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff GAS5 for diagnosis of DM.</p></div><div><h3>Results</h3><p>Our results demonstrate that decreased GAS5 levels in serum were associated with diabetes in a cohort of US military veterans. The ROC analysis revealed an optimal cutoff GAS5 value of less than or equal to 10. qPCR results indicated that individuals with absolute GAS5<!--> <!--><<!--> <!-->10<!--> <!-->ng/μl have almost twelve times higher odds of having diabetes (Exact Odds Ratio [OR]<!--> <!-->=<!--> <!-->11.79 (95% CI: 3.97, 37.26), p<!--> <!--><<!--> <!-->0.001). Analysis indicated area under curve (AUC) of ROC of 0.81 with 85.1% sensitivity and 67.3% specificity in distinguishing non-diabetic from diabetic subjects. The positive predictive value is 71.4%.</p></div><div><h3>Conclusion</h3><p>lncRNA GAS5 levels are correlated to prevalence of T2DM.</p></div><div><h3>General Significance</h3><p>Assessment of GAS5 in serum along with other parameters offers greater accuracy in identifying individuals at-risk for diabetes.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 102-107"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54179688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.05.001
Urszula Razny , Beata Kiec-Wilk , Anna Polus , Joanna Goralska , Malgorzata Malczewska-Malec , Dominika Wnek , Anna Zdzienicka , Anna Gruca , Caroline E. Childs , Maria Kapusta , Krystyna Slowinska-Solnica , Philip C. Calder , Aldona Dembinska-Kiec
{"title":"Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: A randomized placebo controlled trial","authors":"Urszula Razny , Beata Kiec-Wilk , Anna Polus , Joanna Goralska , Malgorzata Malczewska-Malec , Dominika Wnek , Anna Zdzienicka , Anna Gruca , Caroline E. Childs , Maria Kapusta , Krystyna Slowinska-Solnica , Philip C. Calder , Aldona Dembinska-Kiec","doi":"10.1016/j.bbacli.2015.05.001","DOIUrl":"10.1016/j.bbacli.2015.05.001","url":null,"abstract":"<div><h3>Background</h3><p>Caloric restriction and n-3 polyunsaturated fatty acid (PUFA) supplementation protect from some of the metabolic complications. The aim of this study was to assess the influence of a low calorie diet with or without n-3 PUFA supplementation on glucose dependent insulinotropic polypeptide (GIP) output and insulin sensitivity markers in obese subjects.</p></div><div><h3>Methods</h3><p>Obese, non-diabetic subjects (BMI 30–40<!--> <!-->kg/m<sup>2</sup>) and aged 25–65<!--> <!-->yr. were put on low calorie diet (1200–1500<!--> <!-->kcal/day) supplemented with either 1.8<!--> <!-->g/day n-3 PUFA (DHA/EPA, 5:1) (<em>n</em> <!-->=<!--> <!-->24) or placebo capsules (<em>n</em> <!-->=<!--> <!-->24) for three months in a randomized placebo controlled trial. Insulin resistance markers and GIP levels were analysed from samples obtained at fasting and during an oral glucose tolerance test (OGTT).</p></div><div><h3>Results</h3><p>Caloric restriction with n-3 PUFA led to a decrease of insulin resistance index (HOMA-IR) and a significant reduction of insulin output as well as decreased GIP secretion during the OGTT. These effects were not seen with caloric restriction alone. Changes in GIP output were inversely associated with changes in red blood cell EPA content whereas fasting GIP level positively correlated with HOMA-IR index. Blood triglyceride level was lowered by caloric restriction with a greater effect when n-3 PUFA were included and correlated positively with fasting GIP level.</p></div><div><h3>Conclusions</h3><p>Three months of caloric restriction with DHA<!--> <!-->+<!--> <!-->EPA supplementation exerts beneficial effects on insulin resistance, GIP and triglycerides.</p></div><div><h3>General significance</h3><p>Combining caloric restriction and n-3 PUFA improves insulin sensitivity, which may be related to a decrease of GIP levels.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 7-13"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54176808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.06.005
D. Canoy
{"title":"A dictionary of epidemiology — The evolution towards the 6th edition","authors":"D. Canoy","doi":"10.1016/j.bbacli.2015.06.005","DOIUrl":"10.1016/j.bbacli.2015.06.005","url":null,"abstract":"","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 42-43"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.06.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54179217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.06.006
Emma Louise Beckett , Charlotte Martin , Jeong Hwa Choi , Katrina King , Suzanne Niblett , Lyndell Boyd , Konsta Duesing , Zoe Yates , Martin Veysey , Mark Lucock
{"title":"Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker","authors":"Emma Louise Beckett , Charlotte Martin , Jeong Hwa Choi , Katrina King , Suzanne Niblett , Lyndell Boyd , Konsta Duesing , Zoe Yates , Martin Veysey , Mark Lucock","doi":"10.1016/j.bbacli.2015.06.006","DOIUrl":"10.1016/j.bbacli.2015.06.006","url":null,"abstract":"<div><h3>Background</h3><p>Free circulating microRNA (miRNA) in serum may be valuable biomarkers for disease diagnosis and prognosis. miR-21, the archetypal oncogenic miRNA, has been proposed as a biomarker for colorectal cancer and its benign precursor, adenomatous polyps. However, it is now becoming clear that circulating miRNA profiles may be sensitive to lifestyle and environmental influences. Dietary components involved in one-carbon metabolism are particularly well placed to modulate miRNA expression through an influence on DNA methylation pathways.</p></div><div><h3>Methods</h3><p>We investigated the role of methyl group donors (folate, B12, cysteine, homocysteine), polymorphisms of the enzymes of one-carbon metabolism, and serum miR-21 expression in a primary case–control cohort (colonoscopy confirmed adenomatous colon polyps vs controls; n<!--> <!-->=<!--> <!-->253) and a secondary cross-sectional cohort (over 65s; n<!--> <!-->=<!--> <!-->649). The relationships between these parameters and serum miR-21 levels were assessed, stratified by gender.</p></div><div><h3>Conclusions</h3><p>Serum miR-21 expression was related to occurrence of adenomatous polyps in females, but not males. Folate levels and MTHFR-C677T genotype was associated with miR-21 expression in both genders. Additionally, DHFR-19 del and MSR-A66G were associated with miR-21 expression in females and males, respectively. Stimulation with excess folate increased expression of miR-21 in colon cancer cell lines.</p></div><div><h3>General significance</h3><p>This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 45-51"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.06.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54179262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.06.007
Marieke J.H. Begemann , Maya J.L. Schutte , Margot I.E. Slot , Janine Doorduin , P. Roberto Bakker , Neeltje E.M. van Haren , Iris E.C. Sommer
{"title":"Simvastatin augmentation for recent-onset psychotic disorder: A study protocol","authors":"Marieke J.H. Begemann , Maya J.L. Schutte , Margot I.E. Slot , Janine Doorduin , P. Roberto Bakker , Neeltje E.M. van Haren , Iris E.C. Sommer","doi":"10.1016/j.bbacli.2015.06.007","DOIUrl":"10.1016/j.bbacli.2015.06.007","url":null,"abstract":"<div><h3>Background</h3><p>There is ample evidence that inflammatory processes play a role in the pathophysiology of schizophrenia. Randomized controlled trials have shown benefit of some (but not all) anti-inflammatory drugs on symptom severity. So far, these drugs have been given for a relatively short period. Simvastatin combines well-established vascular protection with reduction of the inflammatory status of the brain, thus offering an attractive potential to further improve treatment of schizophrenia and related disorders.</p></div><div><h3>Methods/design</h3><p>We are currently undertaking a double-blind placebo-controlled trial, including 250 patients (18–50<!--> <!-->years of age) whom are diagnosed with a schizophrenia spectrum disorder. Onset of their first psychosis should be no longer than three years ago. Patients are randomized 1:1 to either 40<!--> <!-->mg simvastatin or placebo daily during one year, next to their regular antipsychotic treatment. Primary outcome measures are symptom severity and cognitive decline as measured by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), at baseline and end of treatment. Secondary aims are to establish an attenuation of brain tissue loss and an improvement in general functioning, presence and severity of metabolic syndrome and degree of movement disorders. Lastly, immunological and metabolic parameters are assessed in blood samples to possibly predict treatment response.</p></div><div><h3>Discussion</h3><p>We hypothesize simvastatin to lower symptom severity and to prevent or reduce excessive brain tissue loss and cognitive decline, compared to placebo. We expect that simvastatin will be well-tolerated and lead to decreased prevalence of metabolic syndrome.</p></div><div><h3>Trial registration</h3><p>ClinicalTrails.gov <span>NCT01999309</span><svg><path></path></svg>; EudraCT-number 2013-000834-36.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 52-58"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.06.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54179309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.09.002
Natalie Finner , Anne Quinn , Anna Donovan , Orla O'Leary , Clodagh S. O'Gorman
{"title":"Knowledge of carbohydrate counting and insulin dose calculations in paediatric patients with type 1 diabetes mellitus","authors":"Natalie Finner , Anne Quinn , Anna Donovan , Orla O'Leary , Clodagh S. O'Gorman","doi":"10.1016/j.bbacli.2015.09.002","DOIUrl":"10.1016/j.bbacli.2015.09.002","url":null,"abstract":"<div><h3>Background</h3><p>Patients with type 1 diabetes mellitus (T1DM) who are able to adjust their insulin doses according to the carbohydrate content of a meal, as well as their blood glucose, are likely to have improved glycaemic control (Silverstein et al., 2005). With improved glycaemic control, patients have a lower risk of developing long-term microvascular complications associated with T1DM (Diabetes Control and Complications Trial Research Group, 1993).</p><p>To assess the carbohydrate and insulin knowledge of patients attending our paediatric diabetes clinic at the University Hospital Limerick (UHL), the validated PedCarbQuiz (PCQ) was applied to our clinic population.</p></div><div><h3>Methods</h3><p>This study was completed by applying a questionnaire called the PedCarbQuiz (PCQ) to children exclusively attending our paediatric diabetes clinic at UHL. Of the clinic's 220 patients, 81 participated in the study.</p></div><div><h3>Results</h3><p>The average total PCQ score (%) was higher in the continuous subcutaneous insulin infusion (CSII) group compared with the multiple daily insulin (MDI) injection user group (79.1<!--> <!-->±<!--> <!-->12.1 versus 65.9<!--> <!-->±<!--> <!-->6.6 p<!--> <!-->=<!--> <!-->0.005). The CSII group also had a higher average carbohydrate score (%) compared with the MDI group (79.4<!--> <!-->±<!--> <!-->12.4 versus 66.3<!--> <!-->±<!--> <!-->16.2, p<!--> <!-->=<!--> <!-->0.004).</p></div><div><h3>Conclusions</h3><p>This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is better among patients treated with CSII compared with MDI. However, knowledge in both groups is poorer than in the original US sample.</p></div><div><h3>General significance</h3><p>This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is poorer than in a US based sample, although this knowledge is better among patients treated with CSII compared with MDI. This highlights the need for improved resources for diabetes and carbohydrate counting education for patients with T1DM.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 99-101"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54179736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.10.002
Dunja Westhoff , Joost Witlox , Corneli van Aalst , Rikie M. Scholtens , Sophia E. de Rooij , Barbara C. van Munster , Jos F.M. de Jonghe , Alexander P.J. Houdijk , Piet Eikelenboom , David J. van Westerloo , Diederik van de Beek , Willem A. van Gool , Leo Koenderman
{"title":"Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study","authors":"Dunja Westhoff , Joost Witlox , Corneli van Aalst , Rikie M. Scholtens , Sophia E. de Rooij , Barbara C. van Munster , Jos F.M. de Jonghe , Alexander P.J. Houdijk , Piet Eikelenboom , David J. van Westerloo , Diederik van de Beek , Willem A. van Gool , Leo Koenderman","doi":"10.1016/j.bbacli.2015.10.002","DOIUrl":"10.1016/j.bbacli.2015.10.002","url":null,"abstract":"<div><h3>Background</h3><p>A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery.</p></div><div><h3>Methods</h3><p>Patients (≥<!--> <!-->75<!--> <!-->years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays.</p></div><div><h3>Results</h3><p>In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium.</p></div><div><h3>Conclusion</h3><p>Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings.</p></div><div><h3>General significance</h3><p>This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 115-122"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54180132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-12-01DOI: 10.1016/j.bbacli.2015.06.001
Sergio J. Montano , Jacob Grünler , Deepika Nair , Michael Tekle , Aristi P. Fernandes , Xiang Hua , Arne Holmgren , Kerstin Brismar , Johanna S. Ungerstedt
{"title":"Glutaredoxin mediated redox effects of coenzyme Q10 treatment in type 1 and type 2 diabetes patients","authors":"Sergio J. Montano , Jacob Grünler , Deepika Nair , Michael Tekle , Aristi P. Fernandes , Xiang Hua , Arne Holmgren , Kerstin Brismar , Johanna S. Ungerstedt","doi":"10.1016/j.bbacli.2015.06.001","DOIUrl":"10.1016/j.bbacli.2015.06.001","url":null,"abstract":"<div><p>The possible beneficial effects of coenzyme Q10 (CoQ10) supplementation on disease progression and oxidant status in diabetes remains debated. In the present study, patients with type 1 and type 2 diabetes were treated with oral CoQ10, 100<!--> <!-->mg twice daily for 12<!--> <!-->weeks. We assessed total antioxidant capacity, intra- and extracellular levels of the redox regulating protein glutaredoxin 1 (Grx1), CoQ10, oxidized LDL-cholesterol, lipid profile and HbA1c. We have previously shown that extracellular Grx1 is increased in patients with type 2 diabetes compared to healthy subjects. In the present study, CoQ10 treatment significantly decreased serum Grx1 activity as well as total antioxidant capacity independent of type of diabetes, indicating an improvement to a less oxidized extracellular environment. The effect on serum Grx1 activity was more prominent in patients not on statin treatment. Conversely, intracellular Grx1 activity as well as mRNA levels increased independent of statin treatment. There was a significant improvement in oxidized LDL-cholesterol and lipid profile, with a tendency to improved metabolic control (HbA1c). Additionally, we describe for the first time that CoQ10 is a direct substrate for glutathione, and that Grx1 catalyzes this reaction, thus presenting a novel mechanism for CoQ10 reduction which could explain our findings of an increased intracellular Grx1. In conclusion, 12<!--> <!-->weeks CoQ10 treatment significantly improved the extracellular redox balance and lipid profile, indicating that prolonged treatment may have beneficial effects also on clinical outcome in diabetes.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"4 ","pages":"Pages 14-20"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54179041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-06-01DOI: 10.1016/j.bbacli.2015.02.004
Chun-Hao Huang , Chao-Jen Kuo , Shih-Shin Liang , Shu-Wen Chi , Edward Hsi , Chi-Chao Chen , King-Teh Lee , Shyh-Horng Chiou
{"title":"Onco-proteogenomics identifies urinary S100A9 and GRN as potential combinatorial biomarkers for early diagnosis of hepatocellular carcinoma","authors":"Chun-Hao Huang , Chao-Jen Kuo , Shih-Shin Liang , Shu-Wen Chi , Edward Hsi , Chi-Chao Chen , King-Teh Lee , Shyh-Horng Chiou","doi":"10.1016/j.bbacli.2015.02.004","DOIUrl":"10.1016/j.bbacli.2015.02.004","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC), the major type of liver cancer, is among the most lethal cancers owing to its aggressive nature and frequently late detection. Therefore, the possibility to identify early diagnostic markers could be of significant benefit. Urine has especially become one of the most attractive body fluids in biomarker discovery as it can be obtained non-invasively in large quantities and is stable as compared with other body fluids. To identify potential protein biomarker for early diagnosis of HCC, we explored protein expression profiles in urine from HCC patients and normal controls (n<!--> <!-->=<!--> <!-->44) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry (nanoLC–MS/MS) and stable isotope dimethyl labeling. We have systematically mapped 91 proteins with differential expressions (p<!--> <!--><<!--> <!-->0.05), which included 8 down-regulated microtubule proteins and 83 up-regulated proteins involved in signal and inflammation response. Further integrated proteogenomic approach composed of proteomic, genomic and transcriptomic analysis identified that S100A9 and GRN were co-amplified (p<!--> <!--><<!--> <!-->0.001) and co-expressed (p<!--> <!--><<!--> <!-->0.01) in HCC tumors and urine samples. In addition, the amplifications of <em>S100A9</em> or <em>GRN</em> were found to be associated with poor survival in HCC patients, and their co-amplification was also prognosed worse overall survival than individual ones. Our results suggest that urinary S100A9 and GRN as potential combinatorial biomarkers can be applied to early diagnosis of hepatocellular carcinoma and highlight the utility of onco-proteogenomics for identifying protein markers that can be applied to disease-oriented translational medicine.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"3 ","pages":"Pages 205-213"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.02.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54175880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA clinicalPub Date : 2015-06-01DOI: 10.1016/j.bbacli.2015.05.008
Alessandra M. Campos, Meyrianne Almeida, Valeria N. Figueiredo, Wladimir M. Freitas, Andrei C. Sposito
{"title":"Anthropometric features and myocardial infarction in very elderly people","authors":"Alessandra M. Campos, Meyrianne Almeida, Valeria N. Figueiredo, Wladimir M. Freitas, Andrei C. Sposito","doi":"10.1016/j.bbacli.2015.05.008","DOIUrl":"10.1016/j.bbacli.2015.05.008","url":null,"abstract":"","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"3 ","pages":"Page S3"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.05.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54177248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}