ArticlePloS one2022
Identification and validation of DNA methylation markers to predict axillary lymph node metastasis of breast cancer.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Primary Tumor Epigenetic and Transcriptomic Alterations Associated with Nodal Burden and Metastatic Risk in ER+/HER2- Breast Cancer.International journal of molecular sciences · 2026Article
- Epigenetic Evidence Implies Disturbed Proteostasis and Potentially Protein Aggregation in Suicidality.Biomolecules · 2026Review
- Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.Scientific reports · 2026Article
- Novel Methylation-Based Model for Accurate Diagnosis of Upper Mediastinal Lymph Node Metastasis in Esophagogastric Junction Adenocarcinoma.Cancer science · 2026Article
- Article
- DNA Methylation-Based Diagnosis and Treatment of Breast Cancer.Current cancer drug targets · 2025Review
- RHOF activation of AKT/β-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance.iScience · 2024Article
- Potential Role ofClinical Medicine Insights. Oncology · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAxillary lymph node metastasis (ALNM) is one of the most important prognostic factors for breast cancer patients, and DNA methylation is involved in ALNM of breast cancer. However, the methylation profile of breast cancer ALNM remains unknown.
methodsBreast cancer tissues were collected from patients with and without ALNM. We investigated the genome-wide DNA methylation profile in breast cancer with and without ALNM using reduced representation bisulfite sequencing (RRBS). Then, differentially methylated regions (DMRs) were verified by targeted bisulfite sequencing.
resultsA total of 21491 DMRs were identified between the lymph node positive group and negative group. Compared to the LN-negative breast cancer, LN-positive breast cancer had 10,920 hypermethylated DMRs and 10,571 hypomethylated DMRs. Then, 10 DMRs in the gene promoter region were detected by targeted bisulfite sequencing, these gene included HOXA5, PTOV1-AS1, RHOF, PAX6, GSTP1, RASGRF2, AKR1B1, BNIP3, CRMP1, ING5. Compared with negative lymph node, the promoter methylation levels of RASGRF2, AKR1B1 and CRMP1 increased in positive lymph node, while the promoter methylation level of RHOF decreased in positive lymph node. In addition, Cancer Genome Atlas (TCGA) data showed that RASGRF2, AKR1B1 and CRMP1 were low expressed in breast Cancer tissues, while RHOF was high expressed in breast Cancer tissues. Furthermore, in addition to highly methylated AKR1B1, RASGRF2 and CRMP1 gene promoters, BNIP3, GSTP1, HOXA5 and PAX6 gene promoters were also methylated in ER-positive and HER2-negative breast cancer with ALNM.
conclusionsWhen compared to negative lymph node breast cancer, the positive lymph node breast cancer has a differential methylation status. Promoter methylation of RASGRF2, AKR1B1, CRMP1 and RHOF in lymph node positive breast cancer tissues was significantly different from that in lymph node negative breast cancer tissues. AKR1B1, RASGRF2, CRMP1, BNIP3, GSTP1, HOXA5 and PAX6 genes were methylated in ER-positive and HER2-negative breast cancer with ALNM. The study provides an important biological base for understanding breast cancer with ALNM and developing therapeutic targets for breast cancer with ALNM.
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