Evidence map›Paper›PMID 39563427›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

The prognostic role of ACSL4 in postoperative adjuvant TACE-treated HCC: implications for therapeutic response and mechanistic insights.

Ji Feng, Jin-Lian Bin, Xi-Wen Liao, Yong Wu, Yue Tang, Pei-Zhi Lu, Guang-Zhi Zhu, Qian-Ru Cui, Yock Young Dan, Guo-Huan Yang and 6 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ji Feng *School of Public Health, Fudan University, 130 Dong-An Road, Shanghai, 200032, China.
Jin-Lian Bin *Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Xi-Wen Liao *Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China.
Yong Wu *Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Yue Tang *Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Pei-Zhi LuDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Guang-Zhi ZhuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China.
Qian-Ru CuiDepartment of Physiology, School of Preclinical Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.
Yock Young DanDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
Guo-Huan YangDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Li-Xin LiDepartment of Hepato-Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jing-Huan DengDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
Tao PengDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China. p98720p@163.com.ORCID http://orcid.org/0000-0001-6133-7078
Shing Chuan HooiDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive MD9, Singapore, 117593, Singapore. phshsc@nus.edu.sg.
Jing ZhouDepartment of Physiology, School of Preclinical Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China. gardenia_zhou@hotmail.com.ORCID http://orcid.org/0000-0002-2475-7783
Guo-Dong LuSchool of Public Health, Fudan University, 130 Dong-An Road, Shanghai, 200032, China. lugd@fudan.edu.cn.ORCID http://orcid.org/0000-0001-6056-3196

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) treatment and its underlying mechanisms remain elusive. This study investigates the role of enzymes involved in fatty acid activation, specifically Acyl-CoA synthetase long chain 4 (ACSL4), in HCC patients treated with postoperative adjuvant TACE (PA-TACE) and in nutrient-deprived HCC cells.

methodsWe examined the expression of ACSL4 and its family members in HCC clinical samples and cell lines. The clinical significance of ACSL4, particularly regarding the prognosis of patients treated with PA-TACE, was assessed using two independent HCC cohorts. We further explored the role of ACSL4 in glucose starvation-induced cell death in HCC cells and xenograft mouse models.

resultsAmong the family members, ACSL4 is the most up-regulated enzyme, associated with poor survival in HCC patients, particularly in post-recurrent TACE-treated patients in a Singapore cohort. ACSL4 is essential for HCC cell survival in response to glucose starvation, rather than to hypoxia or to the combination of hypoxia with doxorubicin or cisplatin. ACSL4-mediated arachidonic acid (AA) metabolism supports mitochondrial β-oxidation and energy production. CCAAT/enhancer binding protein α (CEBPA) transcriptionally regulates ACSL4 by binding 3 motifs (-623 to -613, -1197 to -1187 and -1745 to -1735) of ACSL4 upstream promoter region, enhancing its pro-survival effects. Furthermore, canagliflozin (Cana), a clinical-approved drug for type 2 diabetes, mimics glucose starvation and inhibits the growth of ACSL4-low xenograft tumors. Moreover, high ACSL4 or CEBPA expressions correlate with increased recurrence susceptibility after PA-TACE in the China-Guangxi HCC cohort.

conclusionsThe CEBPA-ACSL4 pathway is critical in protecting HCC cells from glucose starvation-induced cell death, suggesting that ACSL4 and CEBPA could serve as valuable prognostic indicators and potential therapeutic targets in the context of PA-TACE treatment for HCC.

Indexed as

Carcinoma, HepatocellularCoenzyme A LigasesLiver NeoplasmsAnimalsCell Line, TumorChemoembolization, TherapeuticFemaleHumansLong-Chain-Fatty-Acid-CoA LigaseMaleMiceMiddle AgedPrognosisXenograft Model Antitumor AssaysCoenzyme A LigasesLong-Chain-Fatty-Acid-CoA LigaseACSL4CanagliflozinGlucose starvationHCCTACE

Identifiers

PMID39563427
PMCPMC11575417

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.