ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma

Feng, Jian; Lu, Peizhi; Zhu, Guangzhi; Hooi, Shing Chuan; Wu, Yong; Huang, Xiaowei; Dai, Hui-Qi; Chen, Pan-hong; Li, Zhongjie; Su, Wenjing; Han, Chuangye; Ye, Xinping; Peng, Tao; Zhou, Jing; Lu, Guo‐Dong

doi:10.1038/s41401-020-0439-x

Cited by 105 publications

(73 citation statements)

References 40 publications

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“…ACSL4 was found to sensitize RSL3-induced ferroptosis through altering the cellular lipid composition ( 8 ). In hepatocellular carcinoma patients who had complete or partial responses to sorafenib-induced ferroptosis, and had higher ACSL4 expression in the pretreated tumor tissues than those who did not respond, ACSL4 was a predictive biomarker for sensitivity of sorafenib in hepatocellular carcinoma ( 41 ). Consistently, ACSL4 suppresses the proliferation of tumor cells through activation of ferroptosis in glioma cells ( 42 ).…”

Section: Mechanism Of Ferroptosismentioning

confidence: 99%

Regulation of ferroptosis by non‑coding RNAs in the development and treatment of cancer (Review)

Luo

Huang

et al. 2020

Oncol Rep

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Ferroptosis, a relatively recently discovered type of cell death that is iron dependent and nonapoptotic, is involved in the accumulation of lipid reactive oxygen species (ROS), and has been shown to serve a vital role in various pathological processes, including those underlying neurodegeneration, ischemic reperfusion injury, acute organ injury, and in particular, tumor biology. Emerging evidence has highlighted the roles of ferroptosis in the development and resistance to chemoradiotherapy in cancer. Recently, an increasing number of studies have shown that non-coding RNAs modulate the process of ferroptotic cell death, and this has further highlighted the potential of regulation of ferroptosis as a means of cancer management. Although these studies have highlighted the critical role of ferroptosis in cancer therapeutics, the roles of ferroptosis induced by non-coding RNAs in cancer development remain unclear. Herein, the current body of knowledge of ferroptosis in cancer is summarized and an overview of the mechanisms of ferroptosis and the functions of non-coding RNAs in regulating ferroptotic cell death are discussed. The future status of ferroptosis in cancer management is deliberated and strategies for treatment of therapy-resistant cancers are discussed.

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Section: Mechanism Of Ferroptosismentioning

confidence: 99%

Regulation of ferroptosis by non‑coding RNAs in the development and treatment of cancer (Review)

Luo

Huang

et al. 2020

Oncol Rep

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“…Sorafenib, the standard first-line therapy against advanced HCC, also exerts cytotoxic effects via the induction of ferroptosis ( Louandre et al, 2013 , 2015 ; Galmiche et al, 2014 ). Several genes have been reported to regulate the sensitivity of HCC cells to sorafenib by enhancing or inhibiting ferroptosis ( Louandre et al, 2015 ; Sun et al, 2016a ; Feng et al, 2020 ). For instance, the down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) attenuates sorafenib-induced lipid peroxidation and ferroptosis ( Feng et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Several genes have been reported to regulate the sensitivity of HCC cells to sorafenib by enhancing or inhibiting ferroptosis ( Louandre et al, 2015 ; Sun et al, 2016a ; Feng et al, 2020 ). For instance, the down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) attenuates sorafenib-induced lipid peroxidation and ferroptosis ( Feng et al, 2020 ). Additionally, the sorafenib-induced up-regulation of metallothionein 1G (MT1G) in HCC suppresses ferroptosis and contributes to the acquired sorafenib resistance of the disease ( Sun et al, 2016a ).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, ferroptosis, a biological process in which immune therapy and sorafenib converge to exert an anti-tumor effect, might have a fundamental impact on the treatment response of HCC. The understanding of the occurrence and regulation of ferroptosis has increased considerably in recent decades; however, only a few studies have explored the ferroptosis-related genes (FRGs) and pathways in HCC ( Louandre et al, 2013 , 2015 ; Carlson et al, 2016 ; Houessinon et al, 2016 ; Sun et al, 2016b ; Bai et al, 2019 ; Qi et al, 2019 ; Feng et al, 2020 ; Kim et al, 2020 ). With the currently available FRGs and immune-related genes (IRGs), and the accumulative data deposited in public databases like The Cancer Genome Atlas (TCGA), it is hypothesized that a prognostic molecular classifier based on the immune response and ferroptosis status might help to identify subgroups of HCC patients with distinct ferroptosis-immune phenotypes and survival profiles.…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Combined Ferroptosis and Immune Prognostic Classifier for Hepatocellular Carcinoma

Liu

Zhang

et al. 2020

Front. Cell Dev. Biol.

102

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BackgroundImmunotherapy and sorafenib exert anti-tumor effects via ferroptosis, but reliable biomarkers for the individual treatment and prognosis prediction of hepatocellular carcinoma (HCC) based on the ferroptosis and immune status remain lacking.MethodsFerroptosis-related genes (FRGs) were identified by downloading data from FerrDb and by searching and reading original articles from PubMed. Immune-related genes (IRGs) were downloaded from ImmPort. Prognostic FRGs and IRGs in the GSE14520 (n = 220) and The Cancer Genome Atlas (TCGA, n = 365) datasets were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction. Ferroptosis expression profiles, the infiltration of immune cells, and the somatic mutation status were analyzed and compared.ResultsTwenty-seven prognostic ferroptosis- and immune-related signatures were included to construct a comprehensive index of ferroptosis and immune status (CIFI). A subgroup of patients was identified as having a high CIFI value, which was associated with a worse prognosis. This subgroup of patients had significantly up-regulated expressions of many suppressors of ferroptosis and higher fractions of immunosuppressive cells, such as cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs). Notably, somatic mutation analysis indicated that high-CIFI patients had higher levels of tumor heterogeneity and higher mutation frequencies of genes like TP53.ConclusionIn this work, a novel prognostic classifier was developed based on ferroptosis- and IRGs in HCC, and this classifier could be used for prognostic prediction and the selection of patients for immunotherapies and targeted therapies.

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“…Several genes have been reported to regulate the sensitivity of HCC cells to sorafenib by enhancing or inhibiting ferroptosis (Louandre et al, 2015;Sun et al, 2016a;Feng et al, 2020). For instance, the down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) attenuates sorafenib-induced lipid peroxidation and ferroptosis (Feng et al, 2020). Additionally, the sorafenib-induced up-regulation of metallothionein 1G (MT1G) in HCC suppresses ferroptosis and contributes to the acquired sorafenib resistance of the disease (Sun et al, 2016a).…”

Section: Introductionmentioning

confidence: 99%

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ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma

Cited by 105 publications

References 40 publications

Regulation of ferroptosis by non‑coding RNAs in the development and treatment of cancer (Review)

Regulation of ferroptosis by non‑coding RNAs in the development and treatment of cancer (Review)

Development and Validation of a Combined Ferroptosis and Immune Prognostic Classifier for Hepatocellular Carcinoma

Data_Sheet_1.docx

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