PMID- 30569112
OWN - NLM
STAT- MEDLINE
DCOM- 20190311
LR  - 20190311
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 41
IP  - 3
DP  - 2019 Mar
TI  - Early decrease in serum amphiregulin or vascular endothelial growth factor levels 
      predicts sorafenib efficacy in hepatocellular carcinoma.
PG  - 2041-2050
LID - 10.3892/or.2018.6922 [doi]
AB  - Sorafenib is the standard of care for the treatment of advanced hepatocellular 
      carcinoma (HCC). However, identifying secreted biomarkers that predict sorafenib 
      efficacy in all HCC patients remains challenging. It was recently reported that 
      sorafenib interferes with protein homeostasis and inhibits global translation in 
      tumour cells. A likely consequence of this inhibition would be the interruption 
      of autocrine loops. The aim of the present study was to investigate the effect of 
      sorafenib on two growth factors implicated in autocrine loops and HCC tumour 
      invasion: amphiregulin (AREG) and vascular endothelial growth factor (VEGF). 
      ELISA, quantitative polymerase chain reaction analysis, western blotting and a 
      cytokine array were performed on HCC cell lines and the prognostic role of these 
      two biomarkers in HCC patients was evaluated. Serum AREG and VEGF levels were 
      assayed by ELISA in 55 patients with advanced HCC treated with sorafenib. It was 
      observed that sorafenib decreased AREG, VEGF and cytokine expression at the 
      transcriptional and post‑transcriptional levels. All HCC patients in our cohort 
      had detectable concentrations of AREG and VEGF both at baseline and after 
      sorafenib treatment. The decreased serum levels of AREG and VEGF after 15 days of 
      sorafenib treatment were significantly associated with better overall and 
      progression‑free survival. The results of the multivariate analysis demonstrated 
      that a decrease in AREG was an independent prognostic indicator of overall 
      survival (hazard ratio, 0.208; 95% confidence interval, 0.173‑0.673; P=0.0003). 
      These results suggest that sorafenib inhibits auto-crine loops and that early 
      decrease in serum AREG or VEGF levels predicts sorafenib efficacy in HCC 
      patients.
FAU - Godin, Corinne
AU  - Godin C
AD  - Equipe CHIMERE, EA 7516, Universite de Picardie Jules Verne, 80054 Amiens, 
      France.
FAU - Bodeau, Sandra
AU  - Bodeau S
AD  - Laboratoire de Biochimie, Centre de Biologie Humaine, CHU Sud, 80054 Amiens, 
      France.
FAU - Saidak, Zuzana
AU  - Saidak Z
AD  - Equipe CHIMERE, EA 7516, Universite de Picardie Jules Verne, 80054 Amiens, 
      France.
FAU - Louandre, Christophe
AU  - Louandre C
AD  - Laboratoire de Biochimie, Centre de Biologie Humaine, CHU Sud, 80054 Amiens, 
      France.
FAU - Francois, Catherine
AU  - Francois C
AD  - EA4294, Universite de Picardie Jules Verne, 80054 Amiens, France.
FAU - Barbare, Jean-Claude
AU  - Barbare JC
AD  - Delegation a la Recherche Clinique et a l'Innovation, CHU Sud, 80054 Amiens, 
      France.
FAU - Coriat, Romain
AU  - Coriat R
AD  - Gastroenterology and Digestive Oncology Unit, Cochin University Hospital, APHP, 
      75006 Paris, France.
FAU - Galmiche, Antoine
AU  - Galmiche A
AD  - Equipe CHIMERE, EA 7516, Universite de Picardie Jules Verne, 80054 Amiens, 
      France.
FAU - Sauzay, Chloe
AU  - Sauzay C
AD  - Equipe CHIMERE, EA 7516, Universite de Picardie Jules Verne, 80054 Amiens, 
      France.
LA  - eng
PT  - Journal Article
DEP - 20181210
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9ZOQ3TZI87 (Sorafenib)
SB  - IM
MH  - Amphiregulin/*blood
MH  - Antineoplastic Agents/*therapeutic use
MH  - Biomarkers, Tumor/*blood
MH  - Carcinoma, Hepatocellular/blood/*drug therapy/mortality
MH  - Cell Line, Tumor
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Liver Neoplasms/blood/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Progression-Free Survival
MH  - Sorafenib/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/*blood
EDAT- 2018/12/21 06:00
MHDA- 2019/03/12 06:00
CRDT- 2018/12/21 06:00
PHST- 2018/06/29 00:00 [received]
PHST- 2018/11/15 00:00 [accepted]
PHST- 2018/12/21 06:00 [pubmed]
PHST- 2019/03/12 06:00 [medline]
PHST- 2018/12/21 06:00 [entrez]
AID - 10.3892/or.2018.6922 [doi]
PST - ppublish
SO  - Oncol Rep. 2019 Mar;41(3):2041-2050. doi: 10.3892/or.2018.6922. Epub 2018 Dec 10.