Evidence map›Paper›PMID 41208199›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Amphiregulin and Epiregulin Confer Radioresistance in Esophageal Squamous Cell Carcinoma Through Oxidative Phosphorylation.

Zhang Lin, Meilian Yao, Xin Xu, Dong Zhang, Lei Xu, Ling Rong, Xiaohang Wang, Yi Duan, Chengkun Chen, Jun Gu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Zhang LinState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Meilian YaoState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Xin XuDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Dong ZhangState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Lei XuDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Ling RongDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Xiaohang WangDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Yi DuanState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Chengkun ChenState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Jun GuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Yao ZhangDepartment of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Qiang LiuDepartment of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Qing YeDepartment of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Gaoping CuiState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.ORCID https://orcid.org/0000-0003-0132-9353
Yujun HaoState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.ORCID https://orcid.org/0000-0001-7340-3925
Xiumei MaDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Funding

Incubating Program for Clinical Innovation of Renji Hospital LYPY-ZD-04National Natural Science Foundation of China 32001046National Natural Science Foundation of China 82073044National Natural Science Foundation of China 82372615Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning GZ2022007Science and Technology Commission of Shanghai Municipality 23ZR1438900Scientific and Technological Research and Talent Cultivation Project of Renji Hospital RJTJ25-QN-065Shanghai Municipal Health and Family Planning Commission 202240172Shanghai Municipal Health and Family Planning Commission 20224Y0221State Key Laboratory of Oncogenes and Related Gene SB24-09State Key Laboratory of Oncogenes and Related Gene ZZ-RCPY-23-26
6 · The paper itself

Abstract

Neoadjuvant chemoradiotherapy (nCRT) improves outcomes for locally advanced esophageal squamous cell carcinoma (ESCC) but exhibits variable efficacy due to heterogeneous radiosensitivity. In this study, metabolic profiling of 59 ESCC patients revealed significant alterations in tricarboxylic acid cycle (TCA) cycle intermediates in pathological complete responders (pCR) vs. non-responders (non-pCR) ESCC patients after nCRT. Functional experiments demonstrated that radioresistant ESCC cells (KYSE410R) exhibited elevated OXPHOS activity, which is reversed by targeting TCA cycle enzymes (CPI-613 (Devimistat), fumarate hydratase-IN-1 (FH-IN-1), etc.) or Oxidative phosphorylation (OXPHOS) inhibitors (IACS-010759, Rotenone, etc.). Irradiation-induced CCAAT Enhancer Binding Protein Beta (CEBPB) upregulated AREG/EREG expression, activating the ERBB/mTOR pathway to promote OXPHOS flux. Knockdown of CEBPB/AREG/EREG disrupted OXPHOS and sensitized ESCC cells to radiation. Clinically, high Amphiregulin/Epiregulin (AREG/EREG) levels correlated with nCRT resistance and poor prognosis. Collectively, the CEBPB/AREG/EREG axis drives radioresistance by reprogramming OXPHOS, suggesting inhibition of this pathway or OXPHOS itself as a promising strategy to enhance ESCC therapeutic responses.

Indexed as

AmphiregulinEpiregulinEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaOxidative PhosphorylationRadiation ToleranceCCAAT-Enhancer-Binding Protein-betaCell Line, TumorChemoradiotherapyFemaleHumansMaleMiddle AgedAmphiregulinCCAAT-Enhancer-Binding Protein-betaCEBPB protein, humanEpiregulinAREGCEBPBEREGesophageal squamous cell carcinomaneoadjuvant chemoradiotherapyOXPHOS

Identifiers

PMID41208199
PMCPMC12866852

What Socratic holds

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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 Socratic graph.