Evidence map›Paper›PMID 39122703›Full record

ArticleCell death & disease2024

Integrative single-cell RNA-seq and spatial transcriptomics analyses reveal diverse apoptosis-related gene expression profiles in EGFR-mutated lung cancer.

Motohiro Izumi, Masanori Fujii, Ikei S Kobayashi, Vivian Ho, Yukie Kashima, Hibiki Udagawa, Daniel B Costa, Susumu S Kobayashi

Abstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
–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

24 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

8 authors.

Motohiro Izumi *Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Masanori Fujii *Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Ikei S KobayashiDepartment of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Vivian HoDepartment of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Yukie KashimaDivision of Translational Genomics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, 277-8577, Japan.
Hibiki UdagawaDivision of Translational Genomics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, 277-8577, Japan.
Daniel B CostaDepartment of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.ORCID 0000-0002-0689-395X
Susumu S KobayashiDepartment of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. skobbidmc@gmail.com.ORCID 0000-0003-2262-4001

Funding

Unmet needs for specific subsets of EGFR mutated lung cancerR37CA218707 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI COSTA, DANIEL BOTELHO · 2018 to 2024
$2.8M
Role of KAT5 in lung cancerR01CA240257 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KOBAYASHI, SUSUMU · 2020 to 2024
$2.0M
LUNGevity Foundation (LUNGevity) 1144389NCI NIH HHS R01 CA240257NCI NIH HHS R37 CA218707
6 · The paper itself

Abstract

In EGFR-mutated lung cancer, the duration of response to tyrosine kinase inhibitors (TKIs) is limited by the development of acquired drug resistance. Despite the crucial role played by apoptosis-related genes in tumor cell survival, how their expression changes as resistance to EGFR-TKIs emerges remains unclear. Here, we conduct a comprehensive analysis of apoptosis-related genes, including BCL-2 and IAP family members, using single-cell RNA sequence (scRNA-seq) and spatial transcriptomics (ST). scRNA-seq of EGFR-mutated lung cancer cell lines captures changes in apoptosis-related gene expression following EGFR-TKI treatment, most notably BCL2L1 upregulation. scRNA-seq of EGFR-mutated lung cancer patient samples also reveals high BCL2L1 expression, specifically in tumor cells, while MCL1 expression is lower in tumors compared to non-tumor cells. ST analysis of specimens from transgenic mice with EGFR-driven lung cancer indicates spatial heterogeneity of tumors and corroborates scRNA-seq findings. Genetic ablation and pharmacological inhibition of BCL2L1/BCL-XL overcome or delay EGFR-TKI resistance. Overall, our findings indicate that BCL2L1/BCL-XL expression is important for tumor cell survival as EGFR-TKI resistance emerges.

Indexed as

ApoptosisErbB ReceptorsLung NeoplasmsMutationSingle-Cell AnalysisAnimalsbcl-X ProteinCell Line, TumorDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceMice, TransgenicProtein Kinase InhibitorsRNA-Seqbcl-X ProteinEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitors

Identifiers

PMID39122703
PMCPMC11316060

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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.