論文

国際誌
2018年9月28日

Inactive immune pathways in triple negative breast cancers that showed resistance to neoadjuvant chemotherapy as inferred from kinase activity profiles.

Oncotarget
  • Takeshi Sawada
  • Riet Hilhorst
  • Savithri Rangarajan
  • Masayuki Yoshida
  • Yuko Tanabe
  • Kenji Tamura
  • Takayuki Kinoshita
  • Tatsu Shimoyama
  • Rinie van Beuningen
  • Rob Ruijtenbeek
  • Hitoshi Tsuda
  • Fumiaki Koizumi
  • 全て表示

9
76
開始ページ
34229
終了ページ
34239
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.18632/oncotarget.26026

About 5% of Triple negative breast cancer patients (TNBCs) who receive neoadjuvant chemotherapy (NAC) experience progressive disease (PD). Few reports are published on TNBCs with PD during NAC, whereas TNBCs that respond to NAC have been well-studied. We investigated kinase activity profiles of TNBCs to explore the biological differences underlying the lack of response to NAC. Among 740 TNBCs, 20 non-responders were identified. Seven non-responders and 10 TNBCs that did not receive NAC (control group) were evaluated. No correlation was observed between NAC response and age, menopausal status, tumor size and axillary lymph node status. Tyrosine kinase activity profiles of TNBC primary tissues from NAC non-responders and the controls were determined with a peptide microarray system. Kinase activity measurements showed that 35 peptides had significantly (p < 0.05) lower phosphorylation in non-responders. ZAP70, LCK, SYK and JAK2 were identified as differentially active upstream kinases. Pathway analysis suggested lower activity in immune-related pathways in non-responders. The number of tumor infiltrating lymphocytes (TILs) was significantly lower (p = 0.0053) in non-responders. Kinases related to the immune system are less activated in non-responders. TILs evaluation suggested that the immune system is hardly active in non-responders and is not activated by NAC treatment.

リンク情報
DOI
https://doi.org/10.18632/oncotarget.26026
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30344939
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188135
ID情報
  • DOI : 10.18632/oncotarget.26026
  • PubMed ID : 30344939
  • PubMed Central 記事ID : PMC6188135

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