HCC Specific Protein Network Involving Interactions of EGFR with A-Raf and Transthyretin: Experimental Analysis and Computational Biology Correlates

2018 ◽  
Vol 18 (8) ◽  
pp. 1163-1176 ◽  
Author(s):  
Maryam Ranjpour ◽  
Deepshikha P. Katare ◽  
Saima Wajid ◽  
Swatantra K. Jain

Background: The network interactions link human disease proteins to regulatory cellular pathways leading to better understanding of protein functions and cellular processes. Revealing the network of signaling pathways in cancer through protein-protein interactions at molecular level enhances our understanding of Hepatocellular Carcinoma (HCC). Objective: A rodent model for study of HCC was developed to identify differentially expressed proteins at very early stage of cancer initiation and throughout its progression. Methodology: HCC was induced by administrating N-Nitrosodiethylamine (DEN) and 2-aminoacetylfluorine (2-AAF) to male Wistar rats. Proteomic approaches such as 2D-Electrophoresis, PD-Quest, MALDI-TOF-MS and Western blot analyses have been used to identify, characterize and validate the differentially expressed proteins in HCC-bearing animals vis-a-vis controls. Results: The step-wise analysis of morphological and histological parameters revealed HCC induction and tumorigenesis at 1 and 4 months after carcinogen treatment, respectively. We report a novel protein network of 735 different proteins out of which eight proteins are characterized by MALDI-TOF-MS analysis soon after HCC was chemically induced in rats. We have analyzed four different novel routes representing the association of experimentally identified proteins with HCC progression. Conclusion: The study suggests that A-Raf, transthyretin and epidermal growth factor receptor play major role in HCC progression by regulating MAPK signaling pathway and lipid metabolism leading to continuous proliferation, neoplastic transformation and tumorigenesis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4297-4297
Author(s):  
Fan Yi Meng ◽  
Shuai Tian ◽  
Jia-ming Tang

Abstract Objective:The distinct proteins of leukemic cells were investigated by proteomics technology between AML-M2a patients before inductive treatments with evidently different duration of first continuous complete remission(CCR1) and AML-M2a patients at replase in order to find their relations with prognosis of AML-M2a. Methods:The bone marrow mononuclear cells(BMMNCs) from 17 cases of AML-M2a patients before inductive treatment were grouped with different duration of CCR1: group A with CCR1 duration exceeded 12 months(11 cases), group B within 6 months(6 cases), and group C was composed of 3 patients at replase among group B. The proteins of BMMNCs from all the patients were separated by two-dimensional electrophoresis, and the part of differentially-expressed proteins were identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS). Results: 6 differentially-expressed proteins were identified between group A and B by MALDI-TOF-MS: tubulin-specific chaperone B, myeloperoxidase, <TT>Solution Structure Of The Ch Domain Of Human Transgelin-2,</TT> glutathione S-transferase, RING zinc finger protein, glyceraldehyde-3-phosphate dehydrogenase.3 differentially-expressed proteins were identified in group C: NAD(P)H dehydrogenase, hypothetical protein, HES1. Conclusion: The distinct proteins of leukemic cells of AML-M2a patients before inductive treatments were involved in prognosis, and the proteins of BMMNCs from patients at replase have changed.


2010 ◽  
Vol 40 (5) ◽  
pp. 369-379 ◽  
Author(s):  
Uta J. E. Thiel ◽  
Ralph Feltens ◽  
Boris Adryan ◽  
Rita Gieringer ◽  
Christoph Brochhausen ◽  
...  

2009 ◽  
Vol 3 (5) ◽  
pp. 574-583 ◽  
Author(s):  
Antonio Qualtieri ◽  
Elena Urso ◽  
Maria Le Pera ◽  
Sabrina Bossio ◽  
Francesca Bernaudo ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Meritxell Deulofeu ◽  
Esteban García-Cuesta ◽  
Eladia María Peña-Méndez ◽  
José Elías Conde ◽  
Orlando Jiménez-Romero ◽  
...  

The high infectivity of SARS-CoV-2 makes it essential to develop a rapid and accurate diagnostic test so that carriers can be isolated at an early stage. Viral RNA in nasopharyngeal samples by RT-PCR is currently considered the reference method although it is not recognized as a strong gold standard due to certain drawbacks. Here we develop a methodology combining the analysis of from human nasopharyngeal (NP) samples by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with the use of machine learning (ML). A total of 236 NP samples collected in two different viral transport media were analyzed with minimal sample preparation and the subsequent mass spectra data was used to build different ML models with two different techniques. The best model showed high performance in terms of accuracy, sensitivity and specificity, in all cases reaching values higher than 90%. Our results suggest that the analysis of NP samples by MALDI-TOF MS and ML is a simple, safe, fast and economic diagnostic test for COVID-19.


2019 ◽  
Vol 19 (2) ◽  
pp. 236-247 ◽  
Author(s):  
Maryam Ranjpour ◽  
Saima Wajid ◽  
Swatantra K. Jain

Background:Identification of events leading to hepatocellular carcinoma (HCC) progression is essential for understanding its pathophysiology. The aims of this study are to identify and characterize differentially expressed proteins in serum of HCC-bearing rats and the corresponding controls during cancer initiation, progression and tumorigenesis.Methods:Chemical carcinogens, N-Nitrosodiethylamine and 2-aminoacetylfluorine are administered to induce HCC to male Wistar rats. The 2D-Electrophoresis and PD-Quest analyses are performed to identify several differentially expressed proteins in serum of HCC-bearing animals. These proteins are further characterized by MALDI-TOF-MS/MS analyses. Using pathwaylinker a HCC-specific network is analyzed among the MALDITOF- MS/MS characterized proteins and their interactors.Results:Carcinogen administration caused inflammation leading to liver injury and HCC development. Liver inflammation was confirmed by increase in the levels of TNF-α and IL-6 in carcinogen treated rats. We report significant increase in expression of two differentially expressed proteins, namely, A-Raf and Fatty Acid 2- Hydroxylase (FA2H), at early stage of HCC initiation, during its progression and at tumor stage. Real-time PCR analysis of mRNA for these proteins confirmed up-regulation of their transcripts. Further, we validated our experimental data with sera of clinically confirmed liver cancer patients.Conclusion:The study suggests that FA2H and A-Raf play a major role in the progression of HCC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22072-e22072
Author(s):  
D. Hawke ◽  
C. Mazouni ◽  
F. André ◽  
K. Baggerly ◽  
K. Baggerly ◽  
...  

e22072 Evaluation of serum profiles changes after neoadjuvant chemotherapy for breast cancer using MALDI-TOF / MS procedure. Background: Response to primary chemotherapy (CT) for breast cancer is heterogeneous among patients and a more tailored treatment would be beneficial in term of reducing exposure to an unnecessary toxicity and optimization of response rates. Mass spectrometry analysis of serum might be helpful in detecting specific changes in response to primary CT. Methods: An applied Biosystems 4700 Proteomics Analyzer matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer was used. A breast cancer cohort of 78 sera samples from 39 HER2 positive patients consisting of matched pretreatment and (6 months) posttreatment samples was used. Blood samples were collected serially before each treatment cycle every 3 weeks of neoadjuvant CT. Samples were divided into those who achieved pathological complete response (pCR, n= 20) and those who had residual disease (RD, n=19). Low-mass differentially expressed peptides were identified using MALDI-TOF/TOF. Results: This procedure yielded a total of 2329 and 3152 peaks respectively, for the responders and non-responders. Biological variation analysis revealed a total of 32 peaks for responders and 643 peaks for non-responders to be differentially regulated with a false discovery rate less than 20%. A total of 8 differentially expressed proteins were identified from their peptides after digestion and LC-MALDI-TOF/TOF. Four in tumors with pCR (AFM, C3, hemopexin, SAP) and four proteins in the RD group were identified (AP1, hemopexin, Complement B, amyloid P component) Conclusions: Our study suggests that MALDI mass spectrometry may be used to predict the tumor response to neoadjuvant chemotherapy. Proteomic analysis may be useful in developing tailored chemotherapy for breast cancer. No significant financial relationships to disclose.


2012 ◽  
Vol 58 (12) ◽  
pp. 1327-1334 ◽  
Author(s):  
Junzhi Qiu ◽  
Yubin Su ◽  
Ivan Gelbǐc ◽  
Yunfeng Qiu ◽  
Xiaocong Xie ◽  
...  

The infection of insects by the entomopathogenic fungus Aschersonia placenta depends on conidia. To identify proteins differentially expressed in A. placenta conidia vs mycelia, we performed a comparative proteomic analysis of A. placenta using 2-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS). We detected 1022 2-DE protein spots in conidia and 1049 in mycelia and analyzed 48 (13 from conidia and 35 from mycelia) using MALDI-TOF-MS. Finally, we identified 28 proteins (7 from conidia and 21 from mycelia). The identified proteins exclusive to conidia included major proteins participating in oxidation–reduction processes and vegetative insecticidal protein 1 (Vip1), a protein that is likely involved in pathogenicity. The identified proteins exclusive to mycelia were those involved in biosynthesis and metabolism, including uridine diphosphate galactopyranose mutase, which might play key roles in hyphal morphogenesis. This report provides the first proteomic analysis of different developmental stages of an Aschersonia species. Although only a small number of proteins were identified, the data represent a useful foundation for future studies concerning the molecular basis of entomopathogenicity in the species A. placenta and in the genus Aschersonia.


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