Overexpression of HIF1α and CAXI predicts poor outcome in early-stage triple negative breast cancer

Min Sun Jin, Hyebin Lee, In Ae Park, Yul Ri Chung, Seock Ah Im, Kyung Hun Lee, Hyeong Gon Moon, Wonshik Han, Kyubo Kim, Tae Yong Kim, Dong Young Noh, Han Suk Ryu

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Dysregulated energy metabolism is one of the main mechanisms for uncontrolled growth in solid tumors. Hypoxia-inducible factor 1-alpha (HIF1α) is a transcription factor implicated in regulating several genes that are responsible for cell metabolism, including carbonic anhydrase IX (CAIX). The aim of this study is to determine the clinical significance of immunohistochemical metabolic alteration in early-stage triple negative breast cancer (TNBC) patients who received cyclophosphamide-based chemotherapy or radiotherapy and those with basal phenotype. Immunohistochemical staining for HIF1α and CAIX was performed to determine the correlation with clinicopathologic variables and survival outcome on tissue microarrays from 270 early-stage TNBC patients. In vitro experiments with multiple human TNBC cell lines, suppression of HIF1α by small interfering RNA (siRNA) significantly reduced CAIX protein expression in all cell lines. In multivariate analyses for different therapeutic modalities and basal phenotype, combined HIF1α and CAIX protein overexpression was significantly associated with disease-free survival in the total cohort (OR = 2.583, P = 0.002), stratified cohorts expressing basal phenotype (OR = 2.234, P = 0.021), and in those patients who received adjuvant chemotherapy (OR = 3.078, P = 0.023) and adjuvant radiotherapy (OR = 2.111, P = 0.050), respectively. In early TNBC, combined HIF1α and CAIX protein expression may serve as an unfavorable prognostic indicator particularly in patients treated with cyclophosphamide-based chemotherapy or radiotherapy as well as those with basal phenotype of breast cancer.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalVirchows Archiv
Volume469
Issue number2
DOIs
StatePublished - 1 Aug 2016

Keywords

  • Adjuvant chemotherapy
  • Adjuvant radiotherapy
  • Basal phenotype
  • Cancer metabolism
  • Poor prognosis
  • Triple negative breast cancer

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