Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease

Räth, Timo; Hage, Lisa; Kügler, Marion; Menendez, Katrin Menendez; Zachoval, Reinhart; Naehrlich, Lutz; Schulz, Richard; Roderfeld, M; Roeb, Elke

doi:10.1371/journal.pone.0058955

Cited by 29 publications

(22 citation statements)

References 64 publications

(85 reference statements)

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“…Proteomics has proven to be useful for elucidating the pathology of and discovering disease markers for hepatocellular carcinoma (HCC). Several studies have employed mass spectrometry techniques to compare sera from HCC patients and their possible correlation with HBV and HCV infections [41] , [42] . Some serum HCC biomarker candidates have been suggested, such as hemopexin [43] , transthyretin, α-fetoprotein [44] , GADPH [45] , alpha-enolase and thrombospondim-1 [7] , [46] and cystatin C [47] .…”

Section: Resultsmentioning

confidence: 99%

Comparative Salivary Proteome of Hepatitis B- and C-Infected Patients

et al. 2014

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Hepatitis B and C virus (HBV and HCV) infections are an important cause of cirrhosis and hepatocellular carcinoma. The natural history has a prominent latent phase, and infected patients may remain undiagnosed; this situation may lead to the continuing spread of these infections in the community. Compelling reasons exist for using saliva as a diagnostic fluid because it meets the demands of being an inexpensive, noninvasive and easy-to-use diagnostic method. Indeed, comparative analysis of the salivary proteome using mass spectrometry is a promising new strategy for identifying biomarkers. Our goal is to apply an Orbitrap-based quantitative approach to explore the salivary proteome profile in HBV- and HCV-infected patients. In the present study, whole saliva was obtained from 20 healthy, (control) 20 HBV-infected and 20 HCV-infected subjects. Two distinct pools containing saliva from 10 subjects of each group were obtained. The samples were ultracentrifuged and fractionated, and all fractions were hydrolyzed (trypsin) and injected into an LTQ-VELOS ORBITRAP. The identification and analyses of peptides were performed using Proteome Discoverer1.3 and ScaffoldQ + v.3.3.1. From a total of 362 distinct proteins identified, 344 proteins were identified in the HBV, 326 in the HCV and 303 in the control groups. Some blood proteins, such as flavin reductase (which converts biliverdin to bilirubin), were detected only in the HCV group. The data showed a reduced presence of complement C3, ceruloplasmin, alpha(1)-acid glycoprotein and alpha(2)-acid glycoprotein in the hepatitis-infected patients. Peptides of serotransferrin and haptoglobin were less detected in the HCV group. This study provides an integrated perspective of the salivary proteome, which should be further explored in future studies targeting specific disease markers for HBV and HCV infection.

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Section: Resultsmentioning

confidence: 99%

Comparative Salivary Proteome of Hepatitis B- and C-Infected Patients

et al. 2014

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“…In ELISA quantifications, TIMP-4 and Endoglin were significantly up-regulated in patients with CFLD and their expression correlated with hepatic staging (63). In summary, according to Debray et al, the diagnostic criteria of CFLD are (Table 2): …”

Section: Resultsmentioning

confidence: 99%

Liver Disease in Cystic Fibrosis: an Update

et al. 2013

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ContextCystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF.Evidence AcquisitionA literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library.ResultsCF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease.ConclusionsLiver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its progression prior to development its related complications.

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“…As a promising way to revolutionize medicine, mass spectral proteomics demonstrates a great potential in identifying novel biomarker patterns from a proteome for diagnosis, prognosis, and other diverse clinical needs [1,2]. However, robust clinical diagnosis from mass spectral data remains an acute challenge in translational bioinformatics due to the special characteristics of proteomics data.…”

Section: Introductionmentioning

confidence: 99%

A Novel Profile Biomarker Diagnosis for Mass Spectral Proteomics

Han

2013

Biocomputing 2014

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Mass spectrometry based proteomics technologies have allowed for a great progress in identifying disease biomarkers for clinical diagnosis and prognosis. However, they face acute challenges from a data reproducibility standpoint, in that no two independent studies have been found to produce the same proteomic patterns. Such reproducibility issues cause the identified biomarker patterns to lose repeatability and prevent real clinical usage. In this work, we propose a profile biomarker approach to overcome this problem from a machine-learning viewpoint by developing a novel derivative component analysis (DCA). As an implicit feature selection algorithm, derivative component analysis enables the separation of true signals from red herrings by capturing subtle data behaviors and removing system noises from a proteomic profile. We further demonstrate its advantages in disease diagnosis by viewing input data as a profile biomarker. The results from our profile biomarker diagnosis suggest an effective solution to overcoming proteomics data's reproducibility problem, present an alternative method for biomarker discovery in proteomics, and provide a good candidate for clinical proteomic diagnosis.

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Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease

Cited by 29 publications

References 64 publications

Comparative Salivary Proteome of Hepatitis B- and C-Infected Patients

Comparative Salivary Proteome of Hepatitis B- and C-Infected Patients

Liver Disease in Cystic Fibrosis: an Update

A Novel Profile Biomarker Diagnosis for Mass Spectral Proteomics

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