Evidence map›Paper›PMID 33718027›Full record

ArticleTranslational lung cancer research2021

The prognostic impact of circulating homeobox A9 methylated DNA in advanced non-small cell lung cancer.

Sara Witting Christensen Wen, Rikke Fredslund Andersen, Torben Frøstrup Hansen, Christa Haugaard Nyhus, Henrik Hager, Ole Hilberg, Anders Jakobsen

Open access · diamondAbstract read
In one paragraph

Article in Translational lung cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 32% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. The prognostic value of methylated ctDNA, soluble PD-L1, and NK-cell activity on the risk of relapse after curative radiotherapy of non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Digital PCR Analysis of Methylated Circulating Tumor DNA.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  7. The Prognostic Impact of Early ctDNA Kinetics in Metastatic Pancreatic Cancer Using the ctDNA-RECIST.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  8. Review
  9. Article
  10. Circulating methylatedOncology letters · 2024
    Article
  11. 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

7 authors at 2 institutions in 1 country.

Sara Witting Christensen WenDepartment of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
Rikke Fredslund AndersenDepartment of Clinical Biochemistry, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
Torben Frøstrup HansenDepartment of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
Christa Haugaard NyhusDepartment of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
Henrik HagerInstitute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.
Ole HilbergInstitute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.
Anders JakobsenDepartment of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
University of Southern Denmark · DKVejle Sygehus · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe homeobox A9 gene encodes a transcription factor, and aberrantly methylated homeobox A9 in the circulation has been suggested as a prognostic marker in early stage non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the prognostic impact of methylated homeobox A9 in plasma from patients with advanced NSCLC.

methodsBlood samples were prospectively collected from patients with NSCLC stage III and IV receiving standard first line chemotherapy. Sampling took place before treatment initiation and subsequently before each treatment cycle. Plasma was stored at -80 °C until analysis. DNA was extracted, and following bisulfite conversion methylated homeobox A9 was analyzed by methylation specific droplet digital polymerase chain reaction. Detection of methylated homeobox A9 was assessed as a binary variable. The primary endpoint was overall survival (OS).

resultsA total of 231 patients were included. At baseline methylated homeobox A9 was detected in 78.5% of the patients with a clear correlation to survival. The median OS for patients with and without detectable methylated homeobox A9 was 7.4 and 11.1 months, respectively [hazard ratio (HR) 1.79, 95% confidence interval (CI): 1.35-2.38, P<0.001]. The difference increased after the first cycle of treatment. At this time point the median OS was 6.2 and 15.6 months for patients with and without detectable methylated homeobox A9, respectively (HR 2.07, 95% CI: 1.58-2.73, P<0.001). The independent prognostic impact of detectable methylated homeobox A9 after one treatment cycle assessed by multiple Cox regression including known prognostic factors resulted in a HR of 3.79 (2.19-6.54, P<0.001) compared to undetectable methylated homeobox A9.

conclusionsMeasurable methylated homeobox A9 after the first treatment cycle may serve as a valuable prognostic marker in patients with advanced NSCLC. Routine clinical application with treatment reconsideration calls for further studies, preferably in prospective clinical trials.

Indexed as

biomarkersCirculating tumor DNAHOXA9methylationnon-small cell lung cancer (NSCLC)

Identifiers

PMID33718027
PMCPMC7947403
OpenAlexW3135779653

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.