Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/180000 |
Resumo: | 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 highperformance 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 cutoffs and combinations for evaluation of performance. |
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Fye, Haddy K. SDrakesmith, Cynthia WrightKramer, Holger B.Camey, Suzi AlvesCosta, Andre Nogueira daJeng, AdamBah, AlasanaKirk, Gregory D.Sharif, Mohamed I. F.Ladep, Nimzing G.Okeke, EdithHainaut, PierreTaylor-Robinson, Simon D.Kessler, Benedikt M.Mendy, Maimuna E.2018-07-03T02:25:42Z20131932-6203http://hdl.handle.net/10183/180000000895230Background: 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 highperformance 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 cutoffs and combinations for evaluation of performance.application/pdfengPloS One. San Francisco. Vol. 8, no. 7 (July 2013), p. e68381, 13 p.Estatística médicaProtein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populationsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000895230.pdf000895230.pdfTexto completo (inglês)application/pdf2430865http://www.lume.ufrgs.br/bitstream/10183/180000/1/000895230.pdfeb83a718c9324fc4beb1e1c2947dd89dMD51TEXT000895230.pdf.txt000895230.pdf.txtExtracted Texttext/plain70645http://www.lume.ufrgs.br/bitstream/10183/180000/2/000895230.pdf.txt1abb3aea002d8a369937fff9e18268afMD5210183/1800002018-07-04 02:26:36.843498oai:www.lume.ufrgs.br:10183/180000Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2018-07-04T05:26:36Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
title |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
spellingShingle |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations Fye, Haddy K. S Estatística médica |
title_short |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
title_full |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
title_fullStr |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
title_full_unstemmed |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
title_sort |
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations |
author |
Fye, Haddy K. S |
author_facet |
Fye, Haddy K. S Drakesmith, Cynthia Wright Kramer, Holger B. Camey, Suzi Alves Costa, Andre Nogueira da Jeng, Adam Bah, Alasana Kirk, Gregory D. Sharif, Mohamed I. F. Ladep, Nimzing G. Okeke, Edith Hainaut, Pierre Taylor-Robinson, Simon D. Kessler, Benedikt M. Mendy, Maimuna E. |
author_role |
author |
author2 |
Drakesmith, Cynthia Wright Kramer, Holger B. Camey, Suzi Alves Costa, Andre Nogueira da Jeng, Adam Bah, Alasana Kirk, Gregory D. Sharif, Mohamed I. F. Ladep, Nimzing G. Okeke, Edith Hainaut, Pierre Taylor-Robinson, Simon D. Kessler, Benedikt M. Mendy, Maimuna E. |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Fye, Haddy K. S Drakesmith, Cynthia Wright Kramer, Holger B. Camey, Suzi Alves Costa, Andre Nogueira da Jeng, Adam Bah, Alasana Kirk, Gregory D. Sharif, Mohamed I. F. Ladep, Nimzing G. Okeke, Edith Hainaut, Pierre Taylor-Robinson, Simon D. Kessler, Benedikt M. Mendy, Maimuna E. |
dc.subject.por.fl_str_mv |
Estatística médica |
topic |
Estatística médica |
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 highperformance 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 cutoffs and combinations for evaluation of performance. |
publishDate |
2013 |
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2013 |
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2018-07-03T02:25:42Z |
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1932-6203 |
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000895230 |
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PloS One. San Francisco. Vol. 8, no. 7 (July 2013), p. e68381, 13 p. |
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