PMID- 37548836
OWN - NLM
STAT- MEDLINE
DCOM- 20231108
LR  - 20231113
IS  - 1534-4681 (Electronic)
IS  - 1068-9265 (Linking)
VI  - 30
IP  - 13
DP  - 2023 Dec
TI  - Transferrin Receptor is Associated with Sensitivity to Ferroptosis Inducers in 
      Hepatocellular Carcinoma.
PG  - 8675-8689
LID - 10.1245/s10434-023-14053-7 [doi]
AB  - PURPOSE: Transferrin receptor (TFR), a membrane protein that has a critical role 
      in the transport of iron into cells, is known to be a ferroptosis-related marker. 
      Although TFR is reported to be abundantly expressed in tumor cells, its 
      relationship with ferroptosis inducers in hepatocellular carcinoma (HCC) remains 
      unclear. METHODS: The authors performed immunohistochemical staining of TFR and 
      divided 350 HCC patients into two groups according to its expression. They 
      analyzed the association between TFR expression and prognosis or 
      clinicopathologic factors. In addition, the regulation of malignant activity and 
      its effect on the efficacy of ferroptosis inducers were investigated in vitro. 
      RESULTS: For this study, 350 patients were divided into TFR-positive (n =180, 
      51.4%) and TFR-negative (n = 170, 48.6%) groups. The TFR-positive group had more 
      hepatitis B surface antigen (HBs-Ag) (p = 0.0230), higher alpha-fetoprotein (AFP) 
      levels (p = 0.0023), higher des-gamma-carboxyprothrombin (DCP) levels (p = 
      0.0327), a larger tumor size (p = 0.0090), greater proportions of Barcelona 
      Clinic Liver Cancer (BCLC) stage B or C (p = 0.0005), poor differentiation (p < 
      0.0001), and microscopic intrahepatic metastasis (p = 0.0066). In the 
      multivariate analyses, TFR expression was an independent prognostic factor in 
      disease-free survival (p = 0.0315). In vitro, TFRC knockdown decreased cell 
      motility. In addition, TFRC knockdown abolished artesunate (AS)-, lenvatinib-, 
      and sorafenib-induced ferroptosis in HCC cell lines. The study demonstrated that 
      simultaneous treatment of AS with multi-kinase inhibitor augmented the 
      ferroptosis-inducing effects of AS in HCC cell lines. CONCLUSION: TFR expression 
      is a poor prognostic factor in HCC, but its expression increases sensitivity to 
      ferroptosis-inducing agents.
CI  - (c) 2023. Society of Surgical Oncology.
FAU - Hiromatsu, Maki
AU  - Hiromatsu M
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Toshida, Katsuya
AU  - Toshida K
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Itoh, Shinji
AU  - Itoh S
AUID- ORCID: 0000-0003-0382-2520
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan. itoh.shinji.453@m.kyushu-u.ac.jp.
FAU - Harada, Noboru
AU  - Harada N
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Kohashi, Kenichi
AU  - Kohashi K
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Oda, Yoshinao
AU  - Oda Y
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Yoshizumi, Tomoharu
AU  - Yoshizumi T
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
LA  - eng
GR  - JP-19K09198/Japan Society for the Promotion of Science London/
PT  - Journal Article
DEP - 20230807
PL  - United States
TA  - Ann Surg Oncol
JT  - Annals of surgical oncology
JID - 9420840
RN  - 0 (Receptors, Transferrin)
SB  - IM
CIN - Ann Surg Oncol. 2023 Dec;30(13):8007-8008. PMID: 37552348
MH  - Humans
MH  - *Carcinoma, Hepatocellular/pathology
MH  - *Liver Neoplasms/pathology
MH  - *Ferroptosis
MH  - Prognosis
MH  - Receptors, Transferrin/analysis
OTO - NOTNLM
OT  - Ferroptosis
OT  - Hepatocellular carcinoma
OT  - Lenvatinib
OT  - Sorafenib
OT  - Transferrin receptor
EDAT- 2023/08/07 13:09
MHDA- 2023/11/08 06:43
CRDT- 2023/08/07 11:12
PHST- 2023/04/28 00:00 [received]
PHST- 2023/06/19 00:00 [accepted]
PHST- 2023/11/08 06:43 [medline]
PHST- 2023/08/07 13:09 [pubmed]
PHST- 2023/08/07 11:12 [entrez]
AID - 10.1245/s10434-023-14053-7 [pii]
AID - 10.1245/s10434-023-14053-7 [doi]
PST - ppublish
SO  - Ann Surg Oncol. 2023 Dec;30(13):8675-8689. doi: 10.1245/s10434-023-14053-7. Epub 
      2023 Aug 7.