Low RUFY3 expression level is associated with lymph node metastasis in older women with invasive breast cancer

Fernando A. Angarita, Masanori Oshi, Akimitsu Yamada, Li Yan, Ryusei Matsuyama, Stephen B. Edge, Itaru Endo, Kazuaki Takabe

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Sentinel lymph node biopsy is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogeneous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women. Methods: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1903) and The Cancer Genome Atlas (TCGA, n = 1046) Pan-cancer study cohorts. Results: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3-predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease-specific survival among older women. Conclusion: Older women with breast cancers who had low expression level of RUFY3 were more frequently diagnosed with LN-positive tumors, which translated into worse prognosis.

Original languageEnglish (US)
Pages (from-to)19-32
Number of pages14
JournalBreast Cancer Research and Treatment
Volume192
Issue number1
DOIs
StatePublished - Feb 2022

Keywords

  • Axillary lymph node
  • Breast cancer
  • Geriatric oncology
  • RUFY3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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