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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Protein Profiling in Hepatocellular Carcinoma by Label-Free Quantitative Proteomics in Two West African Populations
PLoS ONE, Volume 8, No. 7, Article e68381, Year 2013
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Description
Background:Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC.Methods:Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis.Results:Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages.Conclusions:The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance. © 2013 Fye et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3728326/bin/pone.0068381.s001.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3728326/bin/pone.0068381.s002.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3728326/bin/pone.0068381.s003.tiff
Authors & Co-Authors
Fye, Haddy K.S.
United Kingdom, Oxford
Nuffield Department of Medicine
Gambia, Banjul
Medical Research Council Laboratories Gambia
Wright-Drakesmith, Cynthia
United Kingdom, Oxford
Nuffield Department of Medicine
Kramer, Holger B.
United Kingdom, Oxford
Nuffield Department of Medicine
Camey, Suzi Alves
France, Lyon
Centre International de Recherche Sur le Cancer
Brazil, Porto Alegre
Universidade Federal do Rio Grande do Sul
da Costa, André Nogueira
France, Lyon
Centre International de Recherche Sur le Cancer
Jeng, Adam
Gambia, Banjul
Medical Research Council Laboratories Gambia
Bah, Alasana
Gambia, Banjul
Medical Research Council Laboratories Gambia
Kirk, Gregory D.
United States, Baltimore
Johns Hopkins Bloomberg School of Public Health
Sharif, Mohamed I.F.
United Kingdom, London
Imperial College London
Ladep, Nimzing G.
United Kingdom, London
Imperial College London
Okeke, Edith Nonyelum
Nigeria, Jos
University of Jos
Hainaut, Pierre L.
France, Lyon
Centre International de Recherche Sur le Cancer
France, Dardilly
International Prevention Research Institute
Taylor-Robinson, Simon David
United Kingdom, London
Imperial College London
Kessler, Benedikt M.
United Kingdom, Oxford
Nuffield Department of Medicine
Mendy, Maimuna E.
France, Lyon
Centre International de Recherche Sur le Cancer
Gambia, Banjul
Medical Research Council Laboratories Gambia
Statistics
Citations: 19
Authors: 15
Affiliations: 8
Identifiers
Doi:
10.1371/journal.pone.0068381
e-ISSN:
19326203
Research Areas
Cancer
Study Approach
Quantitative
Study Locations
Gambia
Nigeria