Evidence map›Paper›PMID 36685583›Full record

ArticleFrontiers in immunology2022

The relevance between hypoxia-dependent spatial transcriptomics and the prognosis and efficacy of immunotherapy in claudin-low breast cancer.

Huizhi Sun, Yanlei Li, Yanhui Zhang, Xiulan Zhao, Xueyi Dong, Yuhong Guo, Jing Mo, Na Che, Xinchao Ban, Fan Li and 4 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  5. Expression Analysis ofIranian journal of medical sciences · 2026
    Article
  6. Spatial architecture of development and disease.Nature reviews. Genetics · 2026
    Review
  7. Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025
    Review
  8. Article
  9. Tumor Hypoxia: How Conventional Histology Is Reshaped in Breast Carcinoma.International journal of molecular sciences · 2025
    Review
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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

14 authors at 2 institutions in 1 country.

Huizhi SunTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Yanlei LiDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Yanhui ZhangTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Xiulan ZhaoDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Xueyi DongDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Yuhong GuoTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Jing MoDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Na CheDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Xinchao BanDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Fan LiDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Xiaoyu BaiDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Yue LiDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Jihui HaoTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Danfang ZhangDepartment of Pathology, Tianjin Medical University, Tianjin, China.
Tianjin Medical University · CNTianjin Medical University Cancer Institute and Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Hypoxia is an important characteristic of solid tumors. However, spatial transcriptomics (ST) of hypoxia-associated heterogeneity is not clear. Methods: This study integrated Spatial Transcriptomics (ST) with immunofluorescence to demonstrate their spatial distribution in human claudin-low breast cancer MDA-MB-231 engraft. ST spots were clustered with differentially expression genes. The data were combined with hypoxia-specific marker and angiogenesis marker-labeled serial sections to indicate the spatial distribution of hypoxia and hypoxia-inducted transcriptional profile. Moreover, marker genes, cluster-specific hypoxia genes, and their co-essential relationship were identified and mapped in every clusters. The clinicopathological association of marker genes of hypoxia-dependent spatial clusters was explored in 1904 breast cancers from METABRIC database. Results: The tumor from center to periphery were enriched into five hypoxia-dependent subgroups with differentially expressed genes, which were matched to necrosis, necrosis periphery, hypoxic tumor, adaptive survival tumor, and invasive tumor, respectively. Different subgroups demonstrated distinct hypoxia condition and spatial heterogeneity in biological behavior and signaling pathways. Cox regression analysis showed that the invasive tumor (cluster 0) and hypoxic tumor (cluster 6) score could be served as independent prognostic factors in claudin-low patients. KM analysis indicated that high invasive tumor (cluster 0) and hypoxic tumor (cluster 6) score was associated with poor prognoses of claudin-low patients. Further analysis showed that hypoxia-induced immune checkpoints, such as CD276 and NRP1, upregulation in invasive tumor to block infiltration and activation of B cells and CD8+ T cells to change tumor immune microenvironment. Discussion: This study reveals hypoxia-dependent spatial heterogeneity in claudin-low breast cancer and highlights its potential value as a predictive biomarker of clinical outcomes and immunotherapy response. The molecules found in this study also provided potential molecular mechanisms and therapeutic targets for subsequent studies.

Indexed as

Breast NeoplasmsB7 AntigensClaudinsFemaleHumansHypoxiaImmunotherapyPrognosisTranscriptomeTumor MicroenvironmentB7 AntigensCD276 protein, humanClaudinsbreast cancerClaudin-low tumorhypoxiaimmune cell infiltrationspatial transcriptomics

Identifiers

PMID36685583
PMCPMC9846556
OpenAlexW4313584808

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Registered trials

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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.