Fc-Gamma receptor polymorphism and gene expression of peripheral blood mononuclear cells in patients with HER2-positive metastatic breast cancer receiving single-agent trastuzumab

Chikako Shimizu, Kaoru Mogushi, Masaki Suimye Morioka, Harukaze Yamamoto, Kenji Tamura, Yasuhiro Fujiwara, Hiroshi Tanaka

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Aim: The aim of this study was to investigate gene expression in the peripheral blood mononuclear cells (PBMCs) of patients with HER2-positive breast cancer receiving trastuzumab. We also evaluated the effect of Fc-gamma receptor genotype on trastuzumab-driven gene expression. Materials and methods: Gene expression was assessed by microarray analyses before and after administration of single-agent trastuzumab in 34 patients with metastatic HER2-positive breast cancer who were genotyped for Fc-gamma receptor (FcGR) IIA H131R and FcGRIIIA V158F. Gene set enrichment analysis (GSEA) was used to identify the gene sets that were significantly enriched after administration of trastuzumab in patient cohorts categorized by FcGR variant. Results: At baseline three non-immune-related gene sets were identified only in patient cohort of FcGRIIA non-H/H variant. Thirty gene sets were identified in the cohort of FcGRIIIA V/V variants, while no gene set was identified in FcGRIIIA non-V/V variants one week after starting trastuzumab. Eleven gene sets were identified in FcGRIIA H/H variants 8 week after starting trastuzumab, but none in non-H/H variants. Immune-related gene sets were significantly down-regulated after administration of trastuzumab. Conclusion: The response of PBMCs to trastuzumab markedly varied with polymorphisms in FcGRIIA and FcGRIIIA. These results indicate that FcGR polymorphisms contribute to the systemic immune reaction triggered by trastuzumab. Further investigations are needed to clarify the biological effects of FcGR variation on the mechanism of trastuzumab activity.

本文言語English
ページ(範囲)624-632
ページ数9
ジャーナルBreast Cancer
23
4
DOI
出版ステータスPublished - 2016 7月 1

ASJC Scopus subject areas

  • 腫瘍学
  • 放射線学、核医学およびイメージング
  • 薬理学(医学)

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