Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Anne Fages; Talita Duarte-Salles; Magdalena Stepien; Pietro Ferrari; Veronika Fedirko; Clement Pontoizeau; Antonia Trichopoulou; Krasimira Aleksandrova; Anne Tjonneland; Anja Olsen; Franoise Clavel-Chapelon; Marie-Christine Boutron-Ruault; Gianluca Severi; Rudolf Kaaks; Tilman Kuhn; Anna Floegel; Heiner Boeing; Pagona Lagiou; Christina Bamia; Dimitrios Trichopoulos; Domenico Palli; Valeria Pala; Salvatore Panico; Rosario Tumino; Paolo Vineis; H. Bas Bueno-de-Mesquita; Petra H. Peeters; Elisabete Weiderpass; Antonio Agudo; Esther Molina-Montes; Jose Maria Huerta; Eva Ardanaz; Miren Dorronsoro; Klas Sjoberg; Bodil Ohlsson; Kay-Tee Khaw; Nick Wareham; Ruth C. Travis; Julie A. Schmidt; Amanda Cross; Marc Gunter; Elio Riboli; Augustin Scalbert; Isabelle Romieu; Benedicte Elena-Herrmann; Mazda Jenab

doi:10.1186/s12916-015-0462-9

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Anne Fages, Talita Duarte-Salles, Magdalena Stepien, Pietro Ferrari, Veronika Fedirko, Clement Pontoizeau, Antonia Trichopoulou, Krasimira Aleksandrova, Anne Tjonneland, Anja Olsen, Franoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Gianluca Severi, Rudolf Kaaks, Tilman Kuhn, Anna Floegel, Heiner Boeing, Pagona Lagiou, Christina Bamia, Dimitrios TrichopoulosDomenico Palli, Valeria Pala, Salvatore Panico, Rosario Tumino, Paolo Vineis, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Elisabete Weiderpass, Antonio Agudo, Esther Molina-Montes, Jose Maria Huerta, Eva Ardanaz, Miren Dorronsoro, Klas Sjoberg, Bodil Ohlsson, Kay-Tee Khaw, Nick Wareham, Ruth C. Travis, Julie A. Schmidt, Amanda Cross, Marc Gunter, Elio Riboli, Augustin Scalbert, Isabelle Romieu, Benedicte Elena-Herrmann^*, Mazda Jenab

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.

Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort.

Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis.

Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.

Original language	English
Article number	242
Number of pages	14
Journal	BMC Medicine
Volume	13
DOIs	https://doi.org/10.1186/s12916-015-0462-9
Publication status	Published - 23 Sept 2015

Keywords

Epidemiology
European Prospective Investigation into Cancer and Nutrition
Hepatocellular carcinoma
Liver cancer
Metabolomics
Nuclear magnetic resonance
IDENTIFY SERUM BIOMARKERS
FATTY LIVER-DISEASE
TISSUE METABOLOMICS
MASS-SPECTROMETRY
RISK-FACTORS
CANCER
NMR
CIRRHOSIS
METABONOMICS
DISCOVERY

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Fages, A., Duarte-Salles, T., Stepien, M., Ferrari, P., Fedirko, V., Pontoizeau, C., Trichopoulou, A., Aleksandrova, K., Tjonneland, A., Olsen, A., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Severi, G., Kaaks, R., Kuhn, T., Floegel, A., Boeing, H., Lagiou, P., Bamia, C., ... Jenab, M. (2015). Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort. BMC Medicine, 13, Article 242. https://doi.org/10.1186/s12916-015-0462-9

@article{9ad921f9b5a948319d9ed4c178ad7364,

title = "Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort",

abstract = "Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort.Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis.Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.",

keywords = "Epidemiology, European Prospective Investigation into Cancer and Nutrition, Hepatocellular carcinoma, Liver cancer, Metabolomics, Nuclear magnetic resonance, IDENTIFY SERUM BIOMARKERS, FATTY LIVER-DISEASE, TISSUE METABOLOMICS, MASS-SPECTROMETRY, RISK-FACTORS, CANCER, NMR, CIRRHOSIS, METABONOMICS, DISCOVERY",

author = "Anne Fages and Talita Duarte-Salles and Magdalena Stepien and Pietro Ferrari and Veronika Fedirko and Clement Pontoizeau and Antonia Trichopoulou and Krasimira Aleksandrova and Anne Tjonneland and Anja Olsen and Franoise Clavel-Chapelon and Marie-Christine Boutron-Ruault and Gianluca Severi and Rudolf Kaaks and Tilman Kuhn and Anna Floegel and Heiner Boeing and Pagona Lagiou and Christina Bamia and Dimitrios Trichopoulos and Domenico Palli and Valeria Pala and Salvatore Panico and Rosario Tumino and Paolo Vineis and Bueno-de-Mesquita, {H. Bas} and Peeters, {Petra H.} and Elisabete Weiderpass and Antonio Agudo and Esther Molina-Montes and {Maria Huerta}, Jose and Eva Ardanaz and Miren Dorronsoro and Klas Sjoberg and Bodil Ohlsson and Kay-Tee Khaw and Nick Wareham and Travis, {Ruth C.} and Schmidt, {Julie A.} and Amanda Cross and Marc Gunter and Elio Riboli and Augustin Scalbert and Isabelle Romieu and Benedicte Elena-Herrmann and Mazda Jenab",

year = "2015",

month = sep,

day = "23",

doi = "10.1186/s12916-015-0462-9",

language = "English",

volume = "13",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central Ltd.",

}

Fages, A, Duarte-Salles, T, Stepien, M, Ferrari, P, Fedirko, V, Pontoizeau, C, Trichopoulou, A, Aleksandrova, K, Tjonneland, A, Olsen, A, Clavel-Chapelon, F, Boutron-Ruault, M-C, Severi, G, Kaaks, R, Kuhn, T, Floegel, A, Boeing, H, Lagiou, P, Bamia, C, Trichopoulos, D, Palli, D, Pala, V, Panico, S, Tumino, R, Vineis, P, Bueno-de-Mesquita, HB, Peeters, PH, Weiderpass, E, Agudo, A, Molina-Montes, E, Maria Huerta, J, Ardanaz, E, Dorronsoro, M, Sjoberg, K, Ohlsson, B, Khaw, K-T, Wareham, N, Travis, RC, Schmidt, JA, Cross, A, Gunter, M, Riboli, E, Scalbert, A, Romieu, I, Elena-Herrmann, B & Jenab, M 2015, 'Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort', BMC Medicine, vol. 13, 242. https://doi.org/10.1186/s12916-015-0462-9

TY - JOUR

T1 - Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

AU - Fages, Anne

AU - Duarte-Salles, Talita

AU - Stepien, Magdalena

AU - Ferrari, Pietro

AU - Fedirko, Veronika

AU - Pontoizeau, Clement

AU - Trichopoulou, Antonia

AU - Aleksandrova, Krasimira

AU - Tjonneland, Anne

AU - Olsen, Anja

AU - Clavel-Chapelon, Franoise

AU - Boutron-Ruault, Marie-Christine

AU - Severi, Gianluca

AU - Kaaks, Rudolf

AU - Kuhn, Tilman

AU - Floegel, Anna

AU - Boeing, Heiner

AU - Lagiou, Pagona

AU - Bamia, Christina

AU - Trichopoulos, Dimitrios

AU - Palli, Domenico

AU - Pala, Valeria

AU - Panico, Salvatore

AU - Tumino, Rosario

AU - Vineis, Paolo

AU - Bueno-de-Mesquita, H. Bas

AU - Peeters, Petra H.

AU - Weiderpass, Elisabete

AU - Agudo, Antonio

AU - Molina-Montes, Esther

AU - Maria Huerta, Jose

AU - Ardanaz, Eva

AU - Dorronsoro, Miren

AU - Sjoberg, Klas

AU - Ohlsson, Bodil

AU - Khaw, Kay-Tee

AU - Wareham, Nick

AU - Travis, Ruth C.

AU - Schmidt, Julie A.

AU - Cross, Amanda

AU - Gunter, Marc

AU - Riboli, Elio

AU - Scalbert, Augustin

AU - Romieu, Isabelle

AU - Elena-Herrmann, Benedicte

AU - Jenab, Mazda

PY - 2015/9/23

Y1 - 2015/9/23

N2 - Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort.Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis.Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.

AB - Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort.Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis.Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.

KW - Epidemiology

KW - European Prospective Investigation into Cancer and Nutrition

KW - Hepatocellular carcinoma

KW - Liver cancer

KW - Metabolomics

KW - Nuclear magnetic resonance

KW - IDENTIFY SERUM BIOMARKERS

KW - FATTY LIVER-DISEASE

KW - TISSUE METABOLOMICS

KW - MASS-SPECTROMETRY

KW - RISK-FACTORS

KW - CANCER

KW - NMR

KW - CIRRHOSIS

KW - METABONOMICS

KW - DISCOVERY

U2 - 10.1186/s12916-015-0462-9

DO - 10.1186/s12916-015-0462-9

M3 - Article

SN - 1741-7015

VL - 13

JO - BMC Medicine

JF - BMC Medicine

M1 - 242

ER -

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Abstract

Keywords

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