Evidence map›Paper›PMID 40125618›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Methionine Metabolism Dictates PCSK9 Expression and Antitumor Potency of PD-1 Blockade in MSS Colorectal Cancer.

Qi-Long Wang, Zijie Chen, Xiaofei Lu, Huizhen Lin, Huolun Feng, Nuozhou Weng, Liwen Chen, Mengnan Liu, Li Long, Lingjun Huang and 7 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Lynch syndrome withOpen life sciences · 2026
    Article
  8. Review
  9. Crosstalk between mFrontiers in immunology · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
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

17 authors.

Qi-Long WangMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Zijie ChenGuangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Xiaofei LuGuangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Huizhen LinMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Huolun FengDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Nuozhou WengDepartment of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Liwen ChenMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Mengnan LiuMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Li LongMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Lingjun HuangMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Yongmei DengMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Kehong ZhengDepartment of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Xiaojun ZhengMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Yong LiDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Ting CaiMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Jiabin ZhengDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Wei YangMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.ORCID https://orcid.org/0000-0001-9438-7215

Funding

Guangdong Basic and Applied Basic Research Foundation 2019A1515110052Guangdong Basic and Applied Basic Research Foundation 2020A1515011246Guangdong Basic and Applied Basic Research Foundation 2024A1515010664Guangdong Natural Science Funds for Distinguished Young Scholar 2017A030306030Guangzhou Science and Technology Plan Project 202201011490Key-Area Research and Development Program of Guangdong Province 2023B1111020008National Key R&D Program of China 2018YFA0800404National Natural Science Foundation of China 31770931National Natural Science Foundation of China 31800730National Natural Science Foundation of China 81822036National Natural Science Foundation of China 82001745National Natural Science Foundation of China 82372774Natural Science Foundation of Guangdong Province 2018030310293Pearl River Talent Plan of Guangdong Province 2017GC010332
6 · The paper itself

Abstract

Nutrient metabolisms are vitally interrelated to cancer progression and immunotherapy. However, the mechanisms by which nutrient metabolisms interact to remodel immune surveillance within the tumor microenvironment remain largely unexplored. Here it is demonstrated that methionine restriction inhibits the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol homeostasis and a potential target for cancer immunotherapy, in colorectal cancer (CRC) but not in the liver. Mechanistically, methionine is catabolized to S-adenosylmethionine (SAM), promoting mRNA transcription of PCSK9 through increased DNA methyltransferase 1 (DNMT1)-mediated DNA methylation and suppression of sirtuin 6 (SIRT6) expression. Furthermore, both PCSK9 inhibition and dietary methionine restriction (DMR) potentiate PD-1 blockade therapy and foster the infiltration of CD8

Indexed as

Colorectal NeoplasmsMethionineProgrammed Cell Death 1 ReceptorProprotein Convertase 9AnimalsCell Line, TumorDNA MethylationHumansImmune Checkpoint InhibitorsMiceTumor MicroenvironmentImmune Checkpoint InhibitorsMethioninePCSK9 protein, humanPcsk9 protein, mouseProgrammed Cell Death 1 ReceptorProprotein Convertase 9immunotherapy resistancemethionine metabolismMSS colorectal cancerPCSK9

Identifiers

PMID40125618
PMCPMC12097065

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.