Evidence map›Paper›PMID 34228648›Full record

ArticleThe Journal of clinical investigation2021

DNA methylome and transcriptome landscapes of cancer-associated fibroblasts reveal a smoking-associated malignancy index.

Sheng-Fang Su, Hao Ho, Jia-Hua Li, Ming-Fang Wu, Hsu-Chieh Wang, Hsiang-Yuan Yeh, Shuenn-Wen Kuo, Huei-Wen Chen, Chao-Chi Ho, Ker-Chau Li

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Epigenetic regulation of cancer-associated fibroblast heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2023
    Review
  13. Review
  14. Article
  15. 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

10 authors at 5 institutions in 2 countries.

Sheng-Fang SuInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Hao HoInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Jia-Hua LiInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Ming-Fang WuInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Hsu-Chieh WangDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.
Hsiang-Yuan YehSchool of Big Data Management, Soochow University, Taipei, Taiwan.
Shuenn-Wen KuoDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Huei-Wen ChenGraduate Institute of Toxicology, National Taiwan University, College of Medicine, Taipei, Taiwan.
Chao-Chi HoDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.
Ker-Chau LiInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
National Taiwan University · TWNational Taiwan University Hospital · TWInstitute of Statistical Science, Academia Sinica · TWSoochow University · TWUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the β values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine.

Indexed as

EpigenomeTranscriptomeAdultAgedAged, 80 and overCancer-Associated FibroblastsCarcinoma, Non-Small-Cell LungCpG IslandsDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalEpigeneticsGeneticsLung cancerOncology

Identifiers

PMID34228648
PMCPMC8363271
OpenAlexW3180476455

What OpenQuestion holds

Textmetadata
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.