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Clinical Proteomics

Thong Huy Cao, Donald J L Jones, Paulene A Quinn, Daniel Chu Siong Chan, Narayan Hafid, Helen M Parry, Mohapradeep Mohan, Jatinderpal K Sandhu, Stefan D Anker, John G Cleland, Kenneth Dickstein, Gerasimos Filippatos, Hans L Hillege, Marco Metra, Piotr Ponikowski, Nilesh J Samani, Dirk J Van Veldhuisen, Faiez Zannad, Aeilko H Zwinderman, Adriaan A Voors, Chim C Lang, Leong L Ng
Background: Current risk prediction models in heart failure (HF) including clinical characteristics and biomarkers only have moderate predictive value. The aim of this study was to use matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) profiling to determine if a combination of peptides identified with MALDI-MS will better predict clinical outcomes of patients with HF. Methods: A cohort of 100 patients with HF were recruited in the biomarker discovery phase (50 patients who died or had a HF hospital admission vs...
2018: Clinical Proteomics
Sandra Murphy, Margit Zweyer, Michael Henry, Paula Meleady, Rustam R Mundegar, Dieter Swandulla, Kay Ohlendieck
Background: Duchenne muscular dystrophy is a highly complex multi-system disease caused by primary abnormalities in the membrane cytoskeletal protein dystrophin. Besides progressive skeletal muscle degeneration, this neuromuscular disorder is also associated with pathophysiological perturbations in many other organs including the liver. To determine potential proteome-wide alterations in liver tissue, we have used a comparative and mass spectrometry-based approach to study the dystrophic mdx - 4cv mouse model of dystrophinopathy...
2018: Clinical Proteomics
Shadi Toghi Eshghi, Paul Auger, W Rodney Mathews
Advances in the field of targeted proteomics and mass spectrometry have significantly improved assay sensitivity and multiplexing capacity. The high-throughput nature of targeted proteomics experiments has increased the rate of data production, which requires development of novel analytical tools to keep up with data processing demand. Currently, development and validation of targeted mass spectrometry assays require manual inspection of chromatographic peaks from large datasets to ensure quality, a process that is time consuming, prone to inter- and intra-operator variability and limits the efficiency of data interpretation from targeted proteomics analyses...
2018: Clinical Proteomics
Bhaswati Chatterjee, Suman S Thakur
The investigation of post-translational modifications (PTMs) plays an important role for the study of type 2 diabetes. The importance of PTMs has been realized with the advancement of analytical techniques. The challenging detection and analysis of post-translational modifications is eased by different enrichment methods and by high throughput mass spectrometry based proteomics studies. This technology along with different quantitation methods provide accurate knowledge about the changes happening in disease conditions as well as in normal conditions...
2018: Clinical Proteomics
Danni Li, Fangying Huang, Yingchun Zhao, Peter W Villata, Timothy J Griffin, Lin Zhang, Ling Li, Fang Yu
Background: Although total plasma lipoproteome consists of proteins that have shown promises as biomarkers that can identify Alzheimer's disease (AD), effect sizes are modest. The objective of this study is to provide initial proof-of-concept that the plasma lipoproteome more likely differ between AD cases and controls when measured in individual plasma lipoprotein fractions than when measured as total in immunodepleted plasma. Methods: We first developed a targeted proteomics method based on selected reaction monitoring (SRM) and liquid chromatography and tandem mass spectrometry for measurement of 120 tryptic peptides from 79 proteins that are commonly present in plasma lipoproteins...
2018: Clinical Proteomics
Yvonne S Ziegler, James J Moresco, Patricia G Tu, John R Yates, Ann M Nardulli
In recent years, there has been an emphasis on personalizing breast cancer treatment in order to avoid the debilitating side effects caused by broad-spectrum chemotherapeutic drug treatment. Development of personalized medicine requires the identification of proteins that are expressed by individual tumors. Herein, we reveal the identity of plasma membrane proteins that are overexpressed in estrogen receptor α-positive, HER2-positive, and triple negative breast cancer cells. The proteins we identified are involved in maintaining protein structure, intracellular homeostasis, and cellular architecture; enhancing cell proliferation and invasion; and influencing cell migration...
2018: Clinical Proteomics
Gajanan Sathe, Chan Hyun Na, Santosh Renuse, Anil Madugundu, Marilyn Albert, Abhay Moghekar, Akhilesh Pandey
Background: Cerebrospinal fluid (CSF) is an important source of potential biomarkers that affect the brain. Biomarkers for neurodegenerative disorders are needed to assist in diagnosis, monitoring disease progression and evaluating efficacy of therapies. Recent studies have demonstrated the involvement of tyrosine kinases in neuronal cell death. Thus, neurodegeneration in the brain is related to altered tyrosine phosphorylation of proteins in the brain and identification of abnormally phosphorylated tyrosine peptides in CSF has the potential to ascertain candidate biomarkers for neurodegenerative disorders...
2018: Clinical Proteomics
Sung Ho Yun, Edmond Changkyun Park, Sang-Yeop Lee, Hayoung Lee, Chi-Won Choi, Yoon-Sun Yi, Hyun-Joo Ro, Je Chul Lee, Sangmi Jun, Hye-Yeon Kim, Gun-Hwa Kim, Seung Il Kim
Background: Outer membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. OMVs were first identified in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteogenomic analysis. Methods: Purified OMVs from A. baumannii DU202 grown in different antibiotic culture conditions were screened for pathogenic and immunogenic effects, and subjected to quantitative proteomic analysis by one-dimensional electrophoresis and liquid chromatography combined with tandem mass spectrometry (1DE-LC-MS/MS)...
2018: Clinical Proteomics
Xin Liu, Gensheng Liu, Juan Liu, Peng Zhu, Jiahui Wang, Yanwei Wang, Wenting Wang, Ning Li, Xuebo Wang, Chenglin Zhang, Xiaofang Shen, Fujun Liu
Background: In the assisted reproduction, the infertile molecules of spermatozoa from normozoospermic men who underwent the unexplained failure of in vitro fertilization (IVF) due to the lack of sperm binding to the normal zona pellucida, and then achieved pregnancy with the rescue intracytoplasmic sperm injection (R-ICSI) remain unclear. More works are still necessary to explore this male infertile mechanism. Methods: Normozoospermicmen with the IVF pregnancy and normozoospermic men with the R-ICSI pregnancy after the conventional IVF failure were collected...
2018: Clinical Proteomics
Paul D Piehowski, Vladislav A Petyuk, Ryan L Sontag, Marina A Gritsenko, Karl K Weitz, Thomas L Fillmore, Jamie Moon, Hala Makhlouf, Rodrigo F Chuaqui, Emily S Boja, Henry Rodriguez, Jerry S H Lee, Richard D Smith, Danielle M Carrick, Tao Liu, Karin D Rodland
Background: Mass spectrometry-based proteomics has become a powerful tool for the identification and quantification of proteins from a wide variety of biological specimens. To date, the majority of studies utilizing tissue samples have been carried out on prospectively collected fresh frozen or optimal cutting temperature (OCT) embedded specimens. However, such specimens are often difficult to obtain, in limited in supply, and clinical information and outcomes on patients are inherently delayed as compared to banked samples...
2018: Clinical Proteomics
Vanessa Drendel, Bianca Heckelmann, Christoph Schell, Lucas Kook, Martin L Biniossek, Martin Werner, Cordula A Jilg, Oliver Schilling
Background: Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5-7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns. Methods: We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison...
2018: Clinical Proteomics
Antti Jylhä, Janika Nättinen, Ulla Aapola, Alexandra Mikhailova, Matti Nykter, Lei Zhou, Roger Beuerman, Hannu Uusitalo
Background: Advances in mass spectrometry have accelerated biomarker discovery in many areas of medicine. The purpose of this study was to compare two mass spectrometry (MS) methods, isobaric tags for relative and absolute quantitation (iTRAQ) and sequential window acquisition of all theoretical fragment ion spectra (SWATH), for analytical efficiency in biomarker discovery when there are multiple methodological constraints such as limited sample size and several time points for each patient to be analyzed...
2018: Clinical Proteomics
Andrea Padoan, Daniela Basso, Carlo-Federico Zambon, Tommaso Prayer-Galetti, Giorgio Arrigoni, Dania Bozzato, Stefania Moz, Filiberto Zattoni, Rino Bellocco, Mario Plebani
Background: Lower urinary tract symptoms (LUTS) and prostate specific antigen-based parameters seem to have only a limited utility for the differential diagnosis of prostate cancer (PCa). MALDI-TOF/MS peptidomic profiling could be a useful diagnostic tool for biomarker discovery, although reproducibility issues have limited its applicability until now. The current study aimed to evaluate a new MALDI-TOF/MS candidate biomarker. Methods: Within- and between-subject variability of MALDI-TOF/MS-based peptidomic urine and serum analyses were evaluated in 20 and 15 healthy donors, respectively...
2018: Clinical Proteomics
Rita Azevedo, Cristiana Gaiteiro, Andreia Peixoto, Marta Relvas-Santos, Luís Lima, Lúcio Lara Santos, José Alexandre Ferreira
CD44 is a heavily glycosylated membrane receptor playing a key role in cell adhesion, signal transduction and cytoskeleton remodelling. It is also one of the most studied glycoproteins in cancer, frequently explored for stem cell identification, and associated with chemoresistance and metastasis. However, CD44 is a general designation for a large family of splicing variants exhibiting different degrees of glycosylation and, potentially, functionally distinct roles. Moreover, structural diversity associated with ambiguous nomenclature has delayed clinical developments...
2018: Clinical Proteomics
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Nandini A Sahasrabuddhe, Raghothama Chaerkady, Min-Sik Kim, Mary Jo Fackler, Martha Stampfer, Edward Gabrielson, Saraswati Sukumar, Akhilesh Pandey
Background: Cancer-associated fibroblasts (CAFs) are one of the most important components of tumor stroma and play a key role in modulating tumor growth. However, a mechanistic understanding of how CAFs communicate with tumor cells to promote their proliferation and invasion is far from complete. A major reason for this is that most current techniques and model systems do not capture the complexity of signal transduction that occurs between CAFs and tumor cells. Methods: In this study, we employed a stable isotope labeling with amino acids in cell culture (SILAC) strategy to label invasive breast cancer cells, MDA-MB-231, and breast cancer patient-derived CAF this has already been defined above cells...
2018: Clinical Proteomics
Neserin Ali, Stefan Ljunggren, Helen M Karlsson, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Anders Gudmundsson, Jenny Rissler, Jörn Nielsen, Christian H Lindh, Monica Kåredal
Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed...
2018: Clinical Proteomics
Ai-Jie Xin, Yan-Cheng Wu, Hui Lu, Li Cheng, Yi-Hua Gu, Hua Diao, Guo-Wu Chen, Bin Wu, Zheng Li, Sheng-Ce Tao, Xiao-Xi Sun, Hui-Juan Shi
Background: Semen cryopreservation has been widely applied in assisted reproductive technologies and sperm bank, but it causes considerable impairments on sperm quality. It is necessary to find an evaluation indicator for determining the sperm-freezing tolerance. Methods: The glycocalyx of good freezability ejaculates was compared with poor freezability ejaculates by lectin microarray. The significant different lectins were validated by flow cytometry (FACS). To analyze the relationship between the potential biomarker and the tolerance of sperm to cryopreservation, 60 samples with different recovery rates were collected and detected the lectin-binding intensity by FACS...
2018: Clinical Proteomics
Feiyu Shi, Hong Wu, Kai Qu, Qi Sun, Fanni Li, Chengxin Shi, Yaguang Li, Xiaofan Xiong, Qian Qin, Tianyu Yu, Xin Jin, Liang Cheng, Qingxia Wei, Yingchao Li, Junjun She
Background: The development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients. High-throughput proteomics techniques could not only effectively generate a serum peptide profile but also provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer patients. Methods: In this study, we aim to identify potentially discriminating serum biomarkers for GC. In the discovery cohort, we screened potential biomarkers using magnetic-bead-based purification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in 64 samples from 32 GC patients that were taken both pre- and post-operatively and 30 healthy volunteers that served as controls...
2018: Clinical Proteomics
Misol Do, Dohyun Han, Joseph Injae Wang, Hyunsoo Kim, Wooil Kwon, Youngmin Han, Jin-Young Jang, Youngsoo Kim
Background: The application of advanced imaging technologies for identifying pancreatic cysts has become widespread. However, accurately differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy. Methods: Cyst fluid samples were collected from nine IPMN patients (3 LGD, 3 HGD, and 3 invasive IPMN) during their pancreatectomies...
2018: Clinical Proteomics
Anaïs Chauvin, Chang-Shu Wang, Sameh Geha, Perrine Garde-Granger, Alex-Ane Mathieu, Vincent Lacasse, François-Michel Boisvert
Background: Colorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders...
2018: Clinical Proteomics
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