Evidence map›Paper›PMID 42230616›Full record

ArticleNPJ breast cancer2026

Methylation profiling of normal tissue adjacent to breast tumors reveals two distinct groups with divergent tumor microenvironment features.

Hela Koka, Priscilla Ming Yi Lee, Bin Zhu, Feng Wang, Avraam Tapinos, Mustapha Abubakar, Difei Wang, Xiaoyu Wang, Xing Hua, Chad A Highfill and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ breast cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

28 authors.

Hela KokaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Priscilla Ming Yi LeeThe Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
Bin ZhuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Feng WangThe Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
Avraam TapinosManchester Cancer Research Centre, The University of Manchester, Manchester, UK.
Mustapha AbubakarDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Difei WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Xiaoyu WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Xing HuaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Chad A HighfillDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Li FengDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Cherry WuDepartment of Pathology, North District Hospital, Hong Kong, China.
Koon Ho TsangDepartment of Pathology, Yan Chai Hospital, Hong Kong, China.
Yee-Kei TsoiDepartment of Surgery, North District Hospital, Hong Kong, China.
W C ChanDepartment of Surgery, North District Hospital, Hong Kong, China.
Sze Hong LawDepartment of Surgery, North District Hospital, Hong Kong, China.
Ray Ka Wai HungDepartment of Surgery, North District Hospital, Hong Kong, China.
Gary M TseDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Kristine JonesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Aurelie VogtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Amy HutchinsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Belynda HicksDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Montserrat Garcia-ClosasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
David C WedgeManchester Cancer Research Centre, The University of Manchester, Manchester, UK.
Lap Ah TseThe Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China. shelly@cuhk.edu.hk.
Xiaohong R YangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. royang@mail.nih.gov.

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
NIH HHS 75N91019D00024
6 · The paper itself

Abstract

We previously identified diverse genetic evolutionary patterns in whole-genome sequencing of paired normal tissue adjacent to tumor (NAT) and tumor tissues from Hong Kong breast cancer (HKBC) patients. Here, we investigated whether DNA methylation (DNAm) contributes to NAT heterogeneity and shapes the tumor microenvironment (TME). Genome-wide DNAm profiling was performed on paired NAT and tumor tissues from 188 HKBC patients using the Infinium 850 K array. RNA-seq data were available for 76 NATs and 177 tumors. Cellular composition was inferred using MethylCIBERSORT, CIBERSORTx, and EpiDISH, and histopathologic features were assessed on 115 H&E-stained sections. Unsupervised clustering identified two distinct NAT subtypes with divergent TME characteristics. Cluster 1 (N = 139) showed higher epithelial and fibroblast content and enrichment of estrogen response pathways. Cluster 2 (N = 49) exhibited an immune-metabolic phenotype characterized by increased fat and immune cells, stromal disruption, inflammatory pathway activation, and greater macrophage infiltration. Cluster 2 patients also demonstrated significantly younger epigenetic age estimated using multiple epigenetic clocks. These DNAm-defined NAT subtypes and associated TME features were validated in 97 NAT samples from TCGA breast cancer patients. Overall, our findings identify DNAm-driven NAT heterogeneity with distinct TME landscapes, providing new insights into field cancerization and tumor evolution in breast cancer.

Identifiers

PMID42230616
PMCPMC13534499

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