bims-prodis 2018-11-04 papers

Issue of 2018–11–04
four papers selected by
Nancy Gough, Bioserendipity

J Transl Med. 2018 Oct 25. 16(1): 293

iTRAQ-based quantitative analysis of age-specific variations in salivary proteome of caries-susceptible individuals.

Kun Wang, Xiuqing Wang, Sainan Zheng, Yumei Niu, Wenyue Zheng, Xi Qin, Zhongcheng Li, Junyuan Luo, Wentao Jiang, Xuedong Zhou, Wei Li, Linglin Zhang.

BACKGROUND: Human saliva is a protein-rich, easily accessible source of potential biomarkers for the diagnosis of oral and systemic diseases. However, little is known about the changes in salivary proteome associated with aging of patients with dental caries. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) in combination with multiple reaction monitoring mass spectrometry (MRM-MS) to characterize the salivary proteome profiles of subjects of different ages, presenting with and without caries, with the aim of identifying age-related biomarkers for dental caries.
METHODS: Unstimulated whole saliva samples were collected from 40 caries-free and caries-susceptible young adults and elderly individuals. Salivary proteins were extracted, reduced, alkylated, digested with trypsin and then analyzed using iTRAQ-coupled LC-MS/MS, followed by GO annotation, biological pathway analysis, hierarchical clustering analysis, and protein-protein interaction analysis. Candidate verification was then conducted using MRM-MS.
RESULTS: Among 658 salivary proteins identified using tandem mass spectrometry, 435 proteins exhibited altered expression patterns in different age groups with and without caries. Of these proteins, 96 displayed age-specific changes among caries-susceptible adults and elderly individuals, and were mainly associated with salivary secretion pathway, while 110 age-specific proteins were identified among healthy individuals. It was found that the age factor caused significant variations and played an important role in both healthy and cariogenic salivary proteomes. Subsequently, a total of 136 target proteins with complex protein-protein interactions, including 14 age-specific proteins associated with caries, were further successfully validated using MRM analysis. Moreover, non-age-specific proteins (histatin-1 and BPI fold-containing family B member 1) were verified to be important candidate biomarkers for common dental caries.
CONCLUSIONS: Our proteomic analysis performed using the discovery-through-verification pipeline revealed distinct variations caused by age factor in both healthy and cariogenic salivary proteomes, highlighting the significance of age in the great potential of saliva for caries diagnosis and biomarker discovery.

Keywords: Age; Dental caries; MRM; Salivary proteome; iTRAQ

DOI: https://doi.org/10.1186/s12967-018-1669-2

EBioMedicine. 2018 Oct 22. pii: S2352-3964(18)30454-7. [Epub ahead of print]

Histone-lysine N-methyltransferase SETD7 is a potential serum biomarker for colorectal cancer patients.

Baojun Duan, Jun Bai, Jian Qiu, Jianhua Wang, Cong Tong, Xiaofei Wang, Jiyu Miao, Zongfang Li, Wensheng Li, Juan Yang, Chen Huang.

BACKGROUND: There is an urgent need for the identification of new, clinically useful biomarkers of CRC to enhance diagnostic and prognostic capabilities.
METHODS: We performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. We examined SETD7 expression in serum and tissue samples by ELISA and immunohistochemistry respectively and explored the biological function of SETD7 in vitro.
FINDINGS: 85 differentially expressed peptides were identified. Five peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased after surgery. The sensitivity and specificity of SETD7 were 92.17% and 81.08%, with a high diagnostic value (AUC = 0.9477). In addition, SETD7 expression was significantly correlated with tumor stage and microsatellite instability. Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest and increased apoptosis.
INTERPRETATION: Our data indicate that SETD7 could serve as a potential diagnostic and prognostic biomarker for CRC.

Keywords: Colorectal cancer; Proteomics; SETD7; Serum biomarker

DOI: https://doi.org/10.1016/j.ebiom.2018.10.036

J Proteome Res. 2018 Oct 25.

Current Technologies for Complex Glycoproteomics and Their Applications to Biology/Disease-Driven Glycoproteomics.

Hisashi Narimatsu, Hiroyuki Kaji, Sergey Y Vakhrushev, Henrik Clausen, Hui Zhang, Erika Noro, Akira Togayachi, Chiaki Nagai-Okatani, Atsushi Kuno, Xia Zou, Li Cheng, Sheng-Ce Tao, Yangyang Sun.

Glycoproteomics is an important recent advance in the field of glycoscience. In glycomics, glycan structures are comprehensively analyzed after glycans are released from glycoproteins. However, a major limitation of glycomics is the lack of insight into glycoprotein functions. The Biology/Disease-driven Human Proteome Project has a particular focus on biological and medical applications. Glycoproteomics technologies aimed at obtaining a comprehensive understanding of intact glycoproteins, i.e., the kind of glycan structures that are attached to particular amino acids and proteins, have been developed. This Review focuses on the recent progress of the technologies and their applications. First, the methods for large-scale identification of both N- and O-glycosylated proteins are summarized. Next, the progress of analytical methods for intact glycopeptides is outlined. MS/MS-based methods were developed for improving the sensitivity and speed of the mass spectrometer, in parallel with the software for complex spectrum assignment. In addition, a unique approach to identify intact glycopeptides using MS1-based accurate masses is introduced. Finally, as an advance of glycomics, two approaches to provide the spatial distribution of glycans in cells are described, i.e., MS imaging and lectin microarray. These methods allow rapid glycomic profiling of different types of biological samples and thus facilitate glycoproteomics.

Keywords: glycan spatial distribution; glycome mapping; glycoprotein; glycoproteome; glycosylation site-mapping; lectin microarray; mass spectrometry; protein glycosylation; site-specific glycan analysis

DOI: https://doi.org/10.1021/acs.jproteome.8b00515

Curr Top Med Chem. 2018 Oct 24.

Diagnosis of invasive candidiasis: From gold standard methods to promising leading-edge technologies.

Aida Pitarch, Cesar Nombela, Concha Gil.

Invasive candidiasis (IC) poses a major public health problem worldwide. Despite the introduction of new antifungal agents and changes in clinical practices, its morbidity and mortality rates and healthcare costs remain persistently high. This is mainly because of the serious underlying conditions of infected patients (critically ill or severely immunocompromised patients) and the difficulties encountered in early diagnosing this opportunistic mycosis and initiating prompt and appropriate antifungal therapy. In the light of this great clinical challenge, the past decades have witnessed the development of diverse early detection and therapeutic intervention strategies aimed at minimizing the clinical impact and economic burden of this healthcare-associated infection caused by Candida species. Here, we review the currently available methods for IC diagnosis. These encompass (i) gold standard methods (fungal culture and tissue histopathology), (ii) pathogen-derived biomarker detection tests (PCR, protein antigens, mannan, ß-D-glucan and D-arabinitol-based assays), (iii) host-derived biomarker detection tests (Candida albicans germ tube antibodies or CAGTA, anti-mannan antibodies, other infection-specific antibodies, procalcitonin, serum amyloid A, interleukin 17, interleukin 23 and transforming growth factor ß-based assays), (iv) clinical prediction algorithms (Candida score, colonization index and other prediction rules), and (v) leading-edge molecular, proteomic and immunomic technologies (such as peptide nucleic acid-fluorescent in situ hybridization or PNA-FISH, T2 magnetic resonance or T2Candida assay, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or MALDI-TOF MS, among others). Their strengths, utility, limitations as well as combined use to assist in the diagnosis of this life-threatening and costly fungal infection (including candidemia and deep-seated candidiasis) are also discussed.

Keywords: ?-D-glucan; Candida score; Diagnosis; MALDI-TOF ; PNA-FISH; T2Candida; candidemia; invasive candidiasis

DOI: https://doi.org/10.2174/1568026618666181025093146