Evidence map›Paper›PMID 33504904›Full record

ArticleScientific reports2021

Gene expression in circulating tumor cells reveals a dynamic role of EMT and PD-L1 during osimertinib treatment in NSCLC patients.

Aliki Ntzifa, Areti Strati, Galatea Kallergi, Athanasios Kotsakis, Vassilis Georgoulias, Evi Lianidou

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.0field-weighted citation impact, top 4% 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

38 citing papers in PubMed, 54 citations in OpenAlex.

  1. Cancers · 2026
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  5. EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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

6 authors at 4 institutions in 1 country.

Aliki NtzifaAnalysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771, Athens, Greece.
Areti StratiAnalysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771, Athens, Greece.
Galatea KallergiDivision of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, Patras, Greece.
Athanasios KotsakisDepartment of Medical Oncology, General University Hospital of Larissa, Larissa, Greece.
Vassilis GeorgouliasHellenic Oncology Research Group (HORG), Athens, Greece.
Evi LianidouAnalysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771, Athens, Greece. lianidou@chem.uoa.gr.
National and Kapodistrian University of Athens · GRHellenic Oncology Research Group · GRUniversity Hospital of Larissa · GRUniversity of Patras · GR

Funding

Stavros Niarchos Foundation 16785
6 · The paper itself

Abstract

Liquid biopsy is a tool to unveil resistance mechanisms in NSCLC. We studied changes in gene expression in CTC-enriched fractions of EGFR-mutant NSCLC patients under osimertinib. Peripheral blood from 30 NSCLC patients before, after 1 cycle of osimertinib and at progression of disease (PD) was analyzed by size-based CTC enrichment combined with RT-qPCR for gene expression of epithelial (CK-8, CK-18, CK-19), mesenchymal/EMT (VIM, TWIST-1, AXL), stem cell (ALDH-1) markers, PD-L1 and PIM-1. CTCs were also analyzed by triple immunofluorescence for 45 identical blood samples. Epithelial and stem cell profile (p = 0.043) and mesenchymal/EMT and stem cell profile (p = 0.014) at PD were correlated. There was a strong positive correlation of VIM expression with PIM-1 expression at baseline and increased PD-L1 expression levels at PD. AXL overexpression varied among patients and high levels of PIM-1 transcripts were detected. PD-L1 expression was significantly increased at PD compared to baseline (p = 0.016). The high prevalence of VIM positive CTCs suggest a dynamic role of EMT during osimertinib treatment, while increased expression of PD-L1 at PD suggests a theoretical background for immunotherapy in EGFR-mutant NSCLC patients that develop resistance to osimertinib. This observation merits to be further evaluated in a prospective immunotherapy trial.

Indexed as

Aldehyde Dehydrogenase 1 FamilyAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungDNA, ComplementaryFemaleFluorescent Antibody TechniqueHumansMaleNeoplastic Cells, CirculatingProto-Oncogene ProteinsProto-Oncogene Proteins c-pim-1Receptor Protein-Tyrosine KinasesTwist-Related Protein 1VimentinAldehyde Dehydrogenase 1 FamilyAXL protein, humanAxl Receptor Tyrosine KinaseDNA, ComplementaryProto-Oncogene ProteinsProto-Oncogene Proteins c-pim-1Receptor Protein-Tyrosine KinasesTwist-Related Protein 1VimentinVIM protein, human

Identifiers

PMID33504904
PMCPMC7840727
OpenAlexW3124204822

What OpenQuestion holds

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LicenceCC BY
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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.