ArticleJournal of cancer research and clinical oncology2023
Diagnostic performance of RASSF1A and SHOX2 methylation combined with EGFR mutations for differentiation between small pulmonary nodules.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 3 of them syntheses that pooled it.
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Who cites it
9 citing papers in PubMed, 3 syntheses or guidelines pooled it, 10 citations in OpenAlex.
- Clinical value of combinedOncology reviews · 2026Pooled it
- Diagnostic performance of SHOX2 and RASSF1A gene methylation assays in malignant pleural effusion: A systematic review and meta-analysis.Cancer cytopathology · 2025Pooled it
- Distinguishing EGFR mutant subtypes in stage IA non-small cell lung cancer using the presence status of ground glass opacity and final histologic classification: a systematic review and meta-analysis.Frontiers in medicine · 2023Pooled it
- Shox2 and Rassf1a DNA methylation: diagnostic utility and association with clinical stage, histological progression and gene mutational landscape in lung adenocarcinoma.Frontiers in oncology · 2026Article
- Detection ofMolecular and clinical oncology · 2025Article
- Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.MedComm · 2025Review
- Research Progress of Liquid Biopsy Based on DNA Methylation in Tumor Diagnosis and Treatment.Biomolecules · 2024Review
- Combination Analysis ofJournal of Korean medical science · 2024Article
- Utility of SHOX2 and RASSF1A gene methylation detection on the residual cytology material from endobronchial ultrasound-guided transbronchial needle aspiration.CytoJournal · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimAberrant methylation of Ras association domain family 1, isoform A (RASSF1A), and short-stature homeobox gene 2 (SHOX2) promoters has been validated as a pair of valuable biomarkers for diagnosing early lung adenocarcinomas (LUADs). Epidermal growth factor receptor (EGFR) is the key driver mutation in lung carcinogenesis. This study aimed to investigate the aberrant promoter methylation of RASSF1A and SHOX2, and the genetic mutation of EGFR in 258 specimens of early LUADs.
methodsWe retrospectively selected 258 paraffin-embedded samples of pulmonary nodules measuring 2 cm or less in diameter and evaluated the diagnostic performance of individual biomarker assays and multiple panels between noninvasive (group 1) and invasive lesions (groups 2A and 2B). Then, we investigated the interaction between genetic and epigenetic alterations.
resultsThe degree of RASSF1A and SHOX2 promoter methylation and EGFR mutation was significantly higher in invasive lesions than in noninvasive lesions. The three biomarkers distinguished between noninvasive and invasive lesions with reliable sensitivity and specificity: 60.9% sensitivity [95% confidence interval (CI) 52.41-68.78] and 80.0% specificity (95% CI 72.14-86.07). The novel panel biomarkers could further discriminate among three invasive pathological subtypes (area under the curve value > 0.6). The distribution of RASSF1A methylation and EGFR mutation was considerably exclusive in early LUAD (P = 0.002).
conclusionDNA methylation of RASSF1A and SHOX2 is a pair of promising biomarkers, which may be used in combination with other driver alterations, such as EGFR mutation, to support the differential diagnosis of LUADs, especially for stage I.
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