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Biomarker discovery

Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
Navadon Khunlertgit, Byung-Jun Yoon
BACKGROUND: Discovering robust markers for cancer prognosis based on gene expression data is an important yet challenging problem in translational bioinformatics. By integrating additional information in biological pathways or a protein-protein interaction (PPI) network, we can find better biomarkers that lead to more accurate and reproducible prognostic predictions. In fact, recent studies have shown that, "modular markers," that integrate multiple genes with potential interactions can improve disease classification and also provide better understanding of the disease mechanisms...
October 6, 2016: BMC Bioinformatics
Ying Zhang, Xi Wang, Dan Cui, Jun Zhu
The human whole saliva is a vital body fluid to study the physiology and pathology of oral cavity. As a powerful technique for biomarker discovery, mass spectrometry-based proteomic strategy has been introduced to saliva analysis and identified hundreds of proteins and N-glycosylation sites. However, there still lacks of quantitative analysis, which is necessary for biomarker screening and biological researches. In this study, we established an integrated workflow by the combination of stable isotope dimethyl labeling, HILIC enrichment and high resolution mass spectrometry for both quantification of global proteome and N-glycoproteome of human saliva from oral ulcer patients...
October 20, 2016: Proteomics
Voon Kin Chin, Tze Yan Lee, Basir Rusliza, Pei Pei Chong
Candida bloodstream infections remain the most frequent life-threatening fungal disease, with Candida albicans accounting for 70% to 80% of the Candida isolates recovered from infected patients. In nature, Candida species are part of the normal commensal flora in mammalian hosts. However, they can transform into pathogens once the host immune system is weakened or breached. More recently, mortality attributed to Candida infections has continued to increase due to both inherent and acquired drug resistance in Candida, the inefficacy of the available antifungal drugs, tedious diagnostic procedures, and a rising number of immunocompromised patients...
October 18, 2016: International Journal of Molecular Sciences
Madhukar Pai, Mark P Nicol, Catharina C Boehme
Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement...
October 2016: Microbiology Spectrum
Yadveer Singh Grewal, Muhammad J A Shiddiky, Stephen M Mahler, Gerard A Cangelosi, Matt Trau
Rapid progress in disease biomarker discovery has increased the need for robust detection technologies. In the past several years, the designs of many immunoaffinity reagents have focused on lowering costs, improving specificity while also promoting stability. Antibody fragments (scFvs) have long been displayed on the surface of yeast and phage libraries for selection, however the stable production of such fragments presents challenges that hamper their widespread use in diagnostics. Membrane and cell wall proteins similarly suffer from stability problems when solubilized from their native environment...
October 20, 2016: ACS Applied Materials & Interfaces
Ryo Uratani, Yuji Toiyama, Takahito Kitajima, Mikio Kawamura, Junichiro Hiro, Minako Kobayashi, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Takao Mori, Toshio Kato, Ajay Goel, Masato Kusunoki
BACKGROUND: Although there is a growing interest in developing circulating microRNA (miRNA) as noninvasive diagnostic biomarkers for the detection of high-risk colorectal adenomas and early-stage CRCs, but the comparative diagnostic significance of serum vs. exosomal miRNAs remains unexplored. METHODS: Based upon published literature, we performed an initial discovery step by investigating the expression of a miRNA panel in 20 normal colonic mucosa, 27 adenomas, and 19 CRC tissues...
2016: PloS One
Nabil K El Ayoubi, Samia J Khoury
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system. Only a few biomarkers are available in MS clinical practice, such as cerebrospinal fluid oligoclonal bands and immunoglobulin index, serum anti-aquaporin 4 antibodies, and serum anti-John Cunningham virus antibodies. Thus, there is a significant unmet need for biomarkers to assess prognosis, response to therapy, or potential treatment complications. Here we describe emerging biomarkers that are in development, focusing on those from peripheral blood...
October 18, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Jing Gao, Hiroshi Iwamoto, Jukka Koskela, Harri Alenius, Noboru Hattori, Nobuoki Kohno, Tarja Laitinen, Witold Mazur, Ville Pulkkinen
Asthma-COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease. However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized. To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected. This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Peter Nilsson
A number of chronic disease conditions tend to cluster in families with an increased risk in first-degree relatives, but also an increased risk in second-degree relatives. This fact is most often referred to as the heritability (heredity) of these diseases and explained by the influence of genetic factors, or shared environment, even if the more specific details or mechanism leading to disease are not known. New methods have to be explored in screening studies and register linkage studies to define and measure consequences of a positive family history of disease...
September 2016: Journal of Hypertension
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognized as biomarkers of resistance to AR-targeted therapy such as abiraterone or enzalutamide...
October 18, 2016: Journal of Pathology
William Peacock
Dear Editor I read with great interest the manuscript titled "A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults" by Shan R, et al, published in the January issue of the Journal. (1) I do have some questions. The key to marker discovery studies is a precise and accurate description of how the population was identified, including controls. I have significant concerns about the control population in the manuscript. In the presentation the characteristics of the control group are unclear, described only as "not patients in the ED" and with the same exclusion criteria of the other cohorts...
October 18, 2016: Journal of Neurotrauma
Liang Li, Jian-Wei Zhang, Gregory Jenkins, Fang Xie, Erin E Carlson, Brooke L Fridley, William R Bamlet, Gloria M Petersen, Robert R McWilliams, Liewei Wang
BACKGROUND: Pancreatic cancer is a rapidly fatal disease with gemcitabine remaining the first-line therapy. We performed a genotype-phenotype association study to identify biomarkers for predicting gemcitabine treatment outcome. MATERIALS AND METHODS: We selected the top 200 single nucleotide polymorphisms (SNPs) identified from our previous genome-wide association study to associate with overall survival using 400 patients treated with/or without gemcitabine, followed by imputation analysis for regions around the identified SNPs and a replication study using an additional 537 patients by the TaqMan genotyping assay...
October 4, 2016: Pharmacogenetics and Genomics
Xiang Sun, Hongwei Zhang, Longhua Luo, Kezhao Zhong, Yushui Ma, Linlin Fan, Da Fu, Lijuan Wan
The identification of markers for disease diagnostic, prognostic, or predictive purposes will have a great effect in improving patient management. Proteomic‑based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on four patients including clear cell renal cell carcinoma (ccRCC) and paired adjacent non‑cancerous renal tissues using label‑free quantitative proteomics and liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) to identify differentially expressed proteins...
October 11, 2016: Oncology Reports
Jürgen Böhm, Frank Pianka, Nina Stüttgen, Junghyun Rho, Biljana Gigic, Yuzheng Zhang, Nina Habermann, Petra Schrotz-King, Clare Abbenhardt-Martin, Lin Zielske, Paul D Lampe, Alexis Ulrich, Markus K Diener, Cornelia M Ulrich
BACKGROUND: Ventral incisional hernia is the most common long-term complication after an abdominal operation. Among newly diagnosed colorectal cancer patients, we screened the preoperative plasma proteome to explore predictive markers for the development of an incisional hernia. METHODS: We utilized preoperative plasma samples of 72 newly diagnosed colorectal cancer patients who underwent midline incision for tumor resection between 2010 and 2013. A total of 21 patients with incisional hernia occurrence were matched with 51 patients with at least 18 months follow-up without an incisional hernia by sex, age, and body mass index...
October 13, 2016: Surgery
Yun Pang, Ying Tan, Yongzhe Li, Jianchun Zhang, Yongbing Guo, Zhiling Guo, Chengying Zhang, Feng Yu, Ming-Hui Zhao
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overproduction of numerous autoantibodies. Many studies have sought to identify such biomarkers to distinguish patients with active lupus nephritis from SLE patients without renal involvement. Because antibodies to complement C1q appear to be prevalent in patients with active lupus nephritis, we analyzed the frequency of antigenic epitopes of C1q and their clinical significance in a large multicenter study of Chinese patients. The lupus cohort consisted of 210 patients with active lupus nephritis as a discovery cohort, 130 active patients as a validation cohort along with 130 SLE patients without clinical renal involvement, and 100 healthy controls...
October 10, 2016: Kidney International
Yasuhiko Mohri, Yuji Toiyama, Masato Kusunoki
Patient outcomes from gastric cancer vary due to the complexity of stomach carcinogenesis. Recent research using proteomic technologies has targeted components of all of these systems in order to develop biomarkers to aid the early diagnosis of gastric cancer and to assist in prognostic stratification. Areas covered: This review is comprised of evidence obtained from literature searches from PubMed. It covers the evidence of diagnostic, prognostic, and predictive biomarkers for gastric cancer using proteomic technologies, and provides up-to-date references...
October 17, 2016: Expert Review of Proteomics
Marton Szigeti, Andras Guttman
N-glycan profiling of therapeutic glycoproteins is essential to ensure the activity and efficacy of these promising new-generation drugs. The N-linked glycan moieties of these entities highly affect circulation half-life, immunogenicity and receptor-binding activity as well as physicochemical and thermal stability properties. In addition, more than half of the biopharmaceuticals are glycoproteins representing multibillion dollar worldwide business, further emphasizing the importance of their analysis. In the biomedical field, on the other hand, revealing disease-related glycan structure alterations holds the promise of the discovery of new biomarkers for early diagnostics...
2017: Methods in Molecular Biology
Anna Agakova, Frano Vučković, Lucija Klarić, Gordan Lauc, Felix Agakov
Ultra-performance liquid chromatography (UPLC) is the established technology for accurate analysis of IgG Fc N-glycosylation due to its superior sensitivity, resolution, speed, and its capability to provide branch-specific information of glycan species. Correct and cost-efficient preprocessing of chromatographic data is the major prerequisite for subsequent analyses ranging from inference of structural isomers to biomarker discovery and prediction of humoral immune response from characterized changes in glycosylation...
2017: Methods in Molecular Biology
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