Evidence map›Paper›PMID 35688610›Full record

ArticleGut2023

Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment.

Liwen Wang, Yihao Liu, Yuting Dai, Xiaomei Tang, Tong Yin, Chaofu Wang, Ting Wang, Lei Dong, Minmin Shi, Jiejie Qin and 15 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
215citing papers in PubMed, 1 pooled it
23.8field-weighted citation impact, top 1% 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

215 citing papers in PubMed, 1 synthesis or guideline pooled it, 307 citations in OpenAlex.

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155 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 3 institutions in 1 country.

Liwen Wang *Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Yihao Liu *Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Yuting Dai *Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Xiaomei Tang *Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Tong YinShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Chaofu WangDepartment of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Ting WangDepartment of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Lei DongDepartment of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Minmin ShiDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Jiejie QinDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Meilin XueDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Yizhi CaoDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Jia LiuDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Pengyi LiuDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Jinyan HuangShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Chenlei WenDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Jun ZhangDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Zhiwei XuDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Fan BaiBiomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, People's Republic of China.
Xiaxing DengDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Chenghong PengDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Hao ChenDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Lingxi JiangDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China shenby@shsmu.edu.cn jlx12120@rjh.com.cn sjchen@stn.sh.cn.
Saijuan ChenShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China shenby@shsmu.edu.cn jlx12120@rjh.com.cn sjchen@stn.sh.cn.
Baiyong ShenDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China shenby@shsmu.edu.cn jlx12120@rjh.com.cn sjchen@stn.sh.cn.ORCID 0000-0002-3994-248X
Shanghai Jiao Tong University · CNRuijin Hospital · CNPeking University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveInnate immunity plays important roles in pancreatic ductal adenocarcinoma (PDAC), as non-T-cell-enriched tumour. Neutrophils are major players in innate immune system. Here, we aimed to explore the heterogeneity and pro-tumour mechanisms of neutrophils in PDAC.

designWe analysed single-cell transcriptomes of peripheral blood polymorphonuclear leucocytes (PMNs) and tumour-infiltrating immune cells from five patients with PDAC, and performed immunofluorescence/immunohistochemistry staining, multi-omics analysis and

resultsExploration of the heterogeneity of tumour-associated neutrophils (TANs) revealed a terminally differentiated pro-tumour subpopulation (TAN-1) associated with poor prognosis, an inflammatory subpopulation (TAN-2), a population of transitional stage that have just migrated to tumour microenvironment (TAN-3) and a subpopulation preferentially expressing interferon-stimulated genes (TAN-4). Glycolysis signature was upregulated along neutrophil transition trajectory, and TAN-1 was featured with hyperactivated glycolytic activity. The glycolytic switch of TANs was validated by integrative multi-omics approach of transcriptomics, proteomics and metabolomics analysis. Activation of glycolytic activity by LDHA overexpression induced immunosuppression and pro-tumour functions in neutrophil-like differentiated HL-60 (dHL-60) cells. Mechanistic studies revealed BHLHE40, downstream to hypoxia and endoplasmic reticulum stress, was a key regulator in polarisation of neutrophils towards TAN-1 phenotype, and direct transcriptional regulation of BHLHE40 on TAN-1 marker genes was demonstrated by chromatin immunoprecipitation assay. Pro-tumour and immunosuppression functions were observed in dHL-60 cells overexpressing BHLHE40. Importantly, immunohistochemistry analysis of PDAC tissues revealed the unfavourable prognostic value of BHLHE40

conclusionThe dynamic properties of TANs revealed by this study will be helpful in advancing PDAC therapy targeting innate immunity.

Indexed as

Carcinoma, Pancreatic DuctalPancreatic NeoplasmsBasic Helix-Loop-Helix ProteinsHomeodomain ProteinsHumansNeutrophilsSingle-Cell Gene Expression AnalysisTumor MicroenvironmentBasic Helix-Loop-Helix ProteinsBHLHE40 protein, humanHomeodomain Proteinsglucose metabolismimmunotherapypancreatic cancer

Identifiers

PMID35688610
PMCPMC10086491
OpenAlexW4281748563

What OpenQuestion holds

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LicenceCC BY-NC
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.