Evidence map›Paper›PMID 25363290›Full record

ArticleHepatology (Baltimore, Md.)2015

CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation-induced cell death in hepatocellular carcinoma.

Guo-Dong Lu, Yang Huey Ang, Jing Zhou, Jegadeesan Tamilarasi, Benedict Yan, Yaw Chyn Lim, Supriya Srivastava, Manuel Salto-Tellez, Kam M Hui, Han-Ming Shen and 4 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% of its field
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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  13. Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
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  15. Emerging role of lipophagy in liver disorders.Molecular and cellular biochemistry · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 4 countries.

Guo-Dong LuDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; School of Public Health, Guangxi Medical University, China.
Yang Huey Ang
Jing Zhou
Jegadeesan Tamilarasi
Benedict Yan
Yaw Chyn Lim
Supriya Srivastava
Manuel Salto-Tellez
Kam M Hui
Han-Ming Shen
Long N Nguyen
Bryan C Tan
David L Silver
Shing Chuan Hooi
National University of Singapore · SGSignature Research (United States) · USDuke-NUS Medical School · SGGuangxi Medical University · CNNational Cancer Centre Singapore · SGNational University Cancer Institute, Singapore · SGQueen's University Belfast · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelledCCAAT enhancer binding protein α (C/EBPα) plays an essential role in cellular differentiation, growth, and energy metabolism. Here, we investigate the correlation between C/EBPα and hepatocellular carcinoma (HCC) patient outcomes and how C/EBPα protects cells against energy starvation. Expression of C/EBPα protein was increased in the majority of HCCs examined (191 pairs) compared with adjacent nontumor liver tissues in HCC tissue microarrays. Its upregulation was correlated significantly with poorer overall patient survival in both Kaplan-Meier survival (P=0.017) and multivariate Cox regression (P=0.028) analyses. Stable C/EBPα-silenced cells failed to establish xenograft tumors in nude mice due to extensive necrosis, consistent with increased necrosis in human C/EBPα-deficient HCC nodules. Expression of C/EBPα protected HCC cells in vitro from glucose and glutamine starvation-induced cell death through autophagy-involved lipid catabolism. Firstly, C/EBPα promoted lipid catabolism during starvation, while inhibition of fatty acid beta-oxidation significantly sensitized cell death. Secondly, autophagy was activated in C/EBPα-expressing cells, and the inhibition of autophagy by ATG7 knockdown or chloroquine treatment attenuated lipid catabolism and subsequently sensitized cell death. Finally, we identified TMEM166 as a key player in C/EBPα-mediated autophagy induction and protection against starvation.

conclusionThe C/EBPα gene is important in that it links HCC carcinogenesis to autophagy-mediated lipid metabolism and resistance to energy starvation; its expression in HCC predicts poorer patient prognosis.

Indexed as

AdultAgedAnimalsAutophagyCarcinoma, HepatocellularCCAAT-Enhancer-Binding Protein-alphaCell DeathCell Line, TumorHumansLipid MetabolismLiver NeoplasmsMaleMembrane ProteinsMiceMice, Inbred BALB CMiddle AgedCCAAT-Enhancer-Binding Protein-alphaEVA1A protein, humanMembrane Proteins

Identifiers

PMID25363290
PMCPMC4365685
OpenAlexW2155067636

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.