Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west African populations

Autor: Gregory D. Kirk, Simon D. Taylor-Robinson, Pierre Hainaut, Edith N. Okeke, Mohamed I. F. Sharif, Alasana Bah, Maimuna Mendy, Haddy K. S. Fye, Adam Jeng, Benedikt M. Kessler, Andre Nogueira da Costa, Holger B. Kramer, Nimzing G. Ladep, Suzi Alves Camey, Cynthia Wright-Drakesmith
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Proteomics
Liver Cirrhosis
Male
Oncology
Proteome
lcsh:Medicine
Bioinformatics
Biochemistry
Mass Spectrometry
Hepatitis
Estatística médica
0302 clinical medicine
Hemopexin
lcsh:Science
0303 health sciences
Spectrometric Identification of Proteins
Multidisciplinary
Proteomic Databases
Systems Biology
Cancer Risk Factors
Liver Neoplasms
Complement C3
Middle Aged
Hepatitis B
Hepatitis C
3. Good health
Africa
Western
Nutritional Correlates of Cancer
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Medicine
Infectious diseases
Biomarker (medicine)
Female
Cancer Prevention
Cancer Screening
Research Article
Test Evaluation
Adult
medicine.medical_specialty
Carcinoma
Hepatocellular
Quantitative proteomics
Viral and Bacterial Causes of Cancer
Enzyme-Linked Immunosorbent Assay
Viral diseases
Microbiology
Young Adult
03 medical and health sciences
Hepatitis B
Chronic
Diagnostic Medicine
Virology
Internal medicine
Cancer Detection and Diagnosis
Early Detection
Biomarkers
Tumor
medicine
Carcinoma
Humans
Biology
030304 developmental biology
Apolipoprotein A-I
business.industry
lcsh:R
Reproducibility of Results
Cancer
medicine.disease
digestive system diseases
ROC Curve
Viruses and Cancer
Case-Control Studies
alpha 1-Antitrypsin
lcsh:Q
business
Protein Abundance
Zdroj: PLoS ONE, Vol 8, Iss 7, p e68381 (2013)
e68381
PLoS ONE
Repositório Institucional da UFRGS
Universidade Federal do Rio Grande do Sul (UFRGS)
instacron:UFRGS
PLoS ONE; Vol 8
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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