bims-prodis 2018-07-08 papers

Issue of 2018–07–08
four papers selected by
Nancy Gough, Bioserendipity

Sci China Life Sci. 2018 Jun 25.

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model.

Fanshuang Zhang, Yanying Ni, Yuan Yuan, Wei Yin, Youhe Gao.

Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry. A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins. A total of 40 urinary proteins were statistically significant, 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase and aspartate transaminase changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Masson's staining.

Keywords: animal model; biomarker; liver fibrosis; proteomics; urine

DOI: https://doi.org/10.1007/s11427-017-9268-y

Biochim Biophys Acta. 2018 Jun 27. pii: S0925-4439(18)30223-0. [Epub ahead of print]

Serum proteome mapping of EGF transgenic mice reveal mechanistic biomarkers of lung cancer precursor lesions with clinical significance for human adenocarcinomas.

Jürgen Borlak, Florian Länger, Bijon Chatterji.

Atypical adenomatous hyperplasia (AAH) of the lung is a pre-invasive lesion (PL) with high risk of progression to lung cancer (LC). However, the pathways involved are uncertain. We searched for novel mechanistic biomarkers of AAH in an EGF transgenic disease model of lung cancer. Disease regulated proteins were validated by Western immunoblotting and immunohistochemistry (IHC) of control and morphologically altered respiratory epithelium. Translational work involved clinical resection material. Collectively, 68 unique serum proteins were identified by 2DE-MALDI-TOF mass spectrometry and thirteen reached statistical significance (p < 0.05). EGF, amphiregulin and the EGFR endosomal sorting protein VPS28 were induced up to 5-fold while IHC confirmed strong induction of these proteins. Furthermore, ApoA1, α-2-macroglobulin, and vitamin-D binding protein were nearly 6- and 2-fold upregulated in AAH; however, ApoA1 was oppositely regulated in LC to evidence disease stage dependent regulation of this tumour suppressor. Conversely, plasminogen and transthyretin were highly significantly repressed by 3 and 20-fold. IHC confirmed induced ApoA1, Fetuin-B and transthyretin expression to influence calcification, inflammation and tumour-infiltrating macrophages. Moreover, serum ApoA4, ApoH and ApoM were 2-, 2- and 6-fold repressed; however tissue ApoM and sphingosine-1-phosphate receptor expression was markedly induced to suggest a critical role of sphingosine-1-phosphate signalling in PL and malignant transformation. Finally, a comparison of three different LC models revealed common and unique serum biomarkers mechanistically linked to EGFR, cMyc and cRaf signalling. Their validation by IHC on clinical resection material established relevance for distinct human lung pathologies. In conclusion, we identified mechanistic biomarker candidates recommended for in-depth clinical evaluation.

Keywords: Atypical adenomatous hyperplasia; EGF signalling; Human lung pathology; Mechanistic serum biomarkers; Pre-invasive lesion; Transgenic disease model

DOI: https://doi.org/10.1016/j.bbadis.2018.06.019

Biochem Biophys Res Commun. 2018 Jun 30. pii: S0006-291X(18)31466-9. [Epub ahead of print]

Screening and identification of potential protein biomarkers for evaluating the efficacy of intensive therapy in pulmonary tuberculosis.

Ting-Ting Jiang, Li-Ying Shi, Jing Chen, Li-Liang Wei, Meng Li, Yu-Ting Hu, Lin Gan, Chang-Ming Liu, Hui-Hui Tu, Zhi-Bin Li, Wen-Jing Yi, Ji-Cheng Li.

This research aimed to discover potential biomarkers for evaluating the therapeutic efficacy of intensive therapy in pulmonary tuberculosis (TB). Protein profiles in 2-months intensively treated TB patients, untreated TB patients, and healthy controls were investigated with iTRAQ-2DLC-MS/MS technique. 71 differential proteins were identified in 2-months intensively treated TB patients. Significant differences in complement component C7 (CO7), apolipoprotein A-IV (APOA4), apolipoprotein C-II (APOC2), and angiotensinogen (ANGT) were found by ELISA validation. CO7 and ANGT were also found significantly different in sputum negative patients, compared with sputum positive patients after intensive treatment. Clinical analysis showed that after 2-months intensive treatment several indicators were significantly changed, and the one-year cure rate of sputum negative patients were significantly higher than sputum positive patients. Diagnostic models consisting of APOC2, CO7 and APOA4 were established to distinguish intensively treated TB patients from untreated TB patients and healthy controls with the AUC value of 0.910 and 0.935. Meanwhile, ANGT and CO7 were combined to identify sputum negative and sputum positive TB patients after intensive treatment with 89.36% sensitivity, 71.43% specificity, and the AUC value of 0.853. The results showed that APOC2, CO7, APOA4, and ANGT may be potential biomarkers for evaluating the efficacy of intensive anti-TB therapy.

Keywords: Intensive treatment; Potential biomarker; Serum protein; Tuberculosis; iTRAQ

DOI: https://doi.org/10.1016/j.bbrc.2018.06.147

Am J Rhinol Allergy. 2018 Jan 01. 1945892418782233

TREM-1 Neutrophil Activation Pathway Is Suppressed in Eosinophilic Nasal Polyps.

Dawei Wu, Sarina K Mueller, Angela L Nocera, Kristen Finn, Towia A Libermann, Benjamin S Bleier.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 helper T-cell-skewed immune profiles, but the state of the neutrophil activation signaling pathway in CRSwNP is unknown. The purpose of this study was to examine neutrophil activation pathways in the pathogenesis of CRSwNP. Methods Institutional review board approved the study in which tissue proteomes were compared between control (inferior turbinate) and CRSwNP (nasal polyps) (n = 10/group) using an aptamer-based proteomic array and confirmed by whole transcriptomic analysis. Protein expression was analyzed using Student's t test and Benjamini-Hochberg procedures followed by the application of Ingenuity Pathway, MetaCore, and Genemania bioinformatics analyses. Results All the patients with CRSwNP (n = 10) had eosinophilic nasal polyps. Compared with controls, proteins associated with the triggering receptor expressed on myeloid cells 1 (TREM-1) neutrophil activation signaling pathway such as Calcineurin B, zeta chain-associated protein kinase of 70 kD (ZAP70), 14-3-3 protein theta, 14-3-3 protein zeta/delta, protein kinase C delta type (PKC-D), Interleukin (IL)-17B, IL-17B receptor, IL-23, and IL-1B were significantly decreased in CRSwNP (fold change [FC] = -1.60, P = .003; FC = -1.85, P = .040; FC = -1.26, P < .001; FC = -1.05, P = .008; and FC = -1.31, P = .004; FC = -1.22, P < .001; FC = -1.09, P = .022; FC = -1.25, P < .001; and FC = -1.31, P = .014; respectively). In contrast, tissue eosinophil count ( P < .001) and eosinophil-associated proteins such as C-C motif chemokine 17, periostin, and galectin 10 were all significantly increased in CRSwNP (FC = 1.56, P = .009; FC = 3.95, P < .001; and FC = 2.44, P < .001; respectively). Furthermore, the FC of the studied proteins' expression significantly and positively correlated with FC of their mRNA expression ( P = .001, r = .75). Conclusions TREM-1-associated neutrophilic signaling pathway proteins are significantly suppressed in eosinophilic CRSwNP.

Keywords: chronic rhinosinusitis; eosinophil; nasal polyps; neutrophil; proteomic

DOI: https://doi.org/10.1177/1945892418782233