Evidence map›Paper›PMID 32060101›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020

Single-Cell Genomic Characterization Reveals the Cellular Reprogramming of the Gastric Tumor Microenvironment.

Anuja Sathe, Susan M Grimes, Billy T Lau, Jiamin Chen, Carlos Suarez, Robert J Huang, George Poultsides, Hanlee P Ji

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers.

0numbers the graph read from it
0cells of the map it votes in
252citing papers in PubMed
18.6field-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

252 citing papers in PubMed, 374 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

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

8 authors at 3 institutions in 1 country.

Anuja SatheDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-2100-0013
Susan M GrimesStanford Genome Technology Center, Stanford University, Palo Alto, California.
Billy T LauStanford Genome Technology Center, Stanford University, Palo Alto, California.
Jiamin ChenDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California.ORCID 0000-0003-0979-6319
Carlos SuarezDepartment of Pathology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-4531-9723
Robert J HuangDivision of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-0891-7409
George PoultsidesDepartment of Surgery, Stanford University, Stanford, California.
Hanlee P JiDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California. genomics_ji@stanford.edu.
Stanford Medicine · USPalo Alto University · USStanford University · US

Funding

WHOLE YEAST GENOME TRANSCRIPTIONAL AND FUNCTIONAL GENE MAPS--A FEASIBILITY STUDYP01HG000205 · NHGRI · STANFORD UNIVERSITY · PI DAVIS, RONALD WAYNE, HOWE, ROGER THOMAS · 1990 to 2016
$120.9M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Organoid-based Discovery of Oncogenic Drivers and Treatment Resistance MechanismsU01CA217851 · NCI · STANFORD UNIVERSITY · PI CURTIS, CHRISTINA N, JI, HANLEE P · 2017 to 2021
$4.7M
Systematic discovery of neomorph protein-protein interactions in cancer for oncogenic pathway perturbationU01CA217875 · NCI · EMORY UNIVERSITY · PI FU, HAIAN · 2017 to 2021
$4.5M
Statistical Models for Genome Sequencing and AssociationR01HG006137 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI JI, HANLEE P, ZHANG, NANCY R · 2011 to 2022
$4.3M
NCI NIH HHS U01 CA217851NCI NIH HHS U01 CA217875NHGRI NIH HHS P01 HG000205NHGRI NIH HHS R01 HG006137
6 · The paper itself

Abstract

purposeThe tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics have an impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis of gastric cancer together with paired normal tissue and peripheral blood mononuclear cells (PBMC) would identify critical elements of cellular deregulation not apparent with other approaches. EXPERIMENTAL

designscRNA-seq was conducted on seven patients with gastric cancer and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising gastric cancer (32,407 cells), paired normal tissue (18,657 cells), and PBMCs (5,103 cells). Protein expression was validated by multiplex immunofluorescence.

resultsTumor epithelium had copy number alterations, a distinct gene expression program from normal, with intratumor heterogeneity. Gastric cancer TME was significantly enriched for stromal cells, macrophages, dendritic cells (DC), and Tregs. TME-exclusive stromal cells expressed distinct extracellular matrix components than normal. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Tumor DCs had a unique gene expression program compared to PBMC DCs. TME-specific cytotoxic T cells were exhausted with two heterogenous subsets. Helper, cytotoxic T, Treg, and NK cells expressed multiple immune checkpoint or co-stimulatory molecules. Receptor-ligand analysis revealed TME-exclusive intercellular communication.

conclusionsSingle-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the gastric cancer TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states, and intercellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy.

Indexed as

Cellular ReprogrammingGene Expression Regulation, NeoplasticBiomarkers, TumorGene Expression ProfilingHumansLeukocytes, MononuclearSingle-Cell AnalysisStomach NeoplasmsTumor MicroenvironmentBiomarkers, Tumor

Identifiers

PMID32060101
PMCPMC7269843
OpenAlexW3006545951

What OpenQuestion holds

Textmetadata
LicenceTDM
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.