Evidence map›Paper›PMID 30032824›Full record

ArticleLung cancer (Amsterdam, Netherlands)2018

HOXA9 methylation and blood vessel invasion in FFPE tissues for prognostic stratification of stage I lung adenocarcinoma patients.

Delphine Lissa, Teruhide Ishigame, Rintaro Noro, Marguerite J Tucker, Valery Bliskovsky, Steven Shema, Jessica A Beck, Elise D Bowman, Curtis C Harris, Ana I Robles

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

Article in Lung cancer (Amsterdam, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
1.1field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. DNA methylation in pulmonary fibrosis and lung cancer.Expert review of respiratory medicine · 2022
    Review
  10. Article
  11. AhRR methylation contributes to disease progression in urothelial bladder cancer.Cancer biomarkers : section A of Disease markers · 2022
    Article
  12. Article
  13. Article
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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

10 authors at 1 institution in 1 country.

Delphine LissaLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Teruhide IshigameLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Rintaro NoroLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Marguerite J TuckerLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Valery BliskovskyCCR Genomics Core, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Steven ShemaCCR Genomics Core, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Jessica A BeckLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Elise D BowmanLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Curtis C HarrisLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Ana I RoblesLaboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: Ana_Robles@nih.gov.
National Cancer Institute · US

Funding

Molecular Epidemiology of Human Lung CancerZ01BC005480 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HARRIS, CURTIS · 1996 to 2008
$2.3M
Intramural NIH HHS Z01 BC005480
6 · The paper itself

Abstract

objectivesSurgery with curative intent is the standard treatment for stage I lung adenocarcinoma. However, disease recurrence occurs in a third of patients. Prognostic biomarkers are needed to improve postoperative management. Here, we evaluate the utility of Homeobox A9 (HOXA9) promoter methylation, alone or in combination with Blood Vessel Invasion (BVI) assessment, for prognostic stratification of stage I lung adenocarcinoma patients. MATERIALS AND

methodsWe developed a Droplet Digital PCR (ddPCR) assay to measure HOXA9 promoter methylation in formalin-fixed paraffin-embedded (FFPE) biospecimens generated during routine pathology. The prognostic value of HOXA9 promoter methylation and BVI, alone and in combination, was evaluated by Kaplan-Meier survival and Cox regression analyses in a cohort of 177 stage I lung adenocarcinoma patients from the NCI-MD study.

resultsThe ddPCR assay showed linearity, sensitivity and specificity for measuring HOXA9 promoter methylation down to 0.1% methylated DNA input. The HOXA9 promoter was methylated de novo in FFPE tumors (P < 0.0001). High methylation was independently associated with worse cancer-specific survival (Hazard Ratio [HR], 3.37; P = 0.0002) and identified high-risk stage IA and IB patients. Addition of this molecular marker improved a risk model comprised of clinical and pathologic parameters (age, gender, race, stage, and smoking history; nested likelihood ratio test; P = 0.0004) and increased the C-index from 0.60 (95% CI 0.51-0.69) to 0.68 (0.60-0.76). High methylation tumors displayed high frequency of TP53 mutations and other molecular characteristics associated with aggressiveness. BVI was independently associated with poor outcome (HR, 2.62; P = 0.054). A score that combined BVI with HOXA9 promoter methylation further stratified high-risk patients (trend P = 0.0001 comparing 0, 1 or 2 positive markers).

conclusionsddPCR can be used to quantify HOXA9 promoter methylation in FFPE samples. Alone or combined with BVI in a prognostic classifier, HOXA9 promoter methylation could potentially inform the clinical management of patients with early-stage lung adenocarcinoma.

Indexed as

AdenocarcinomaAgedBiomarkers, TumorBlood VesselsCase-Control StudiesCohort StudiesDNA MethylationFemaleHomeodomain ProteinsHumansLung NeoplasmsMaleMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingBiomarkers, Tumorhomeobox protein HOXA9Homeodomain ProteinsDroplet digital PCRHOXA9 promoter methylationLung adenocarcinomaPost-operative recurrencePrognostic biomarkers

Identifiers

PMID30032824
PMCPMC6662588
OpenAlexW2803218637

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.