Gene expression of adipokines and adipokine receptors in the tumor microenvironment: associations of lower expression with more aggressive breast tumor features

Adana A.M. Llanos, Song Yao, Amartya Singh, John B. Aremu, Hossein Khiabanian, Yong Lin, Coral Omene, Angela R. Omilian, Thaer Khoury, Chi Chen Hong, Shridar Ganesan, David J. Foran, Michael J. Higgins, Christine B. Ambrosone, Elisa V. Bandera, Kitaw Demissie

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Limited epidemiologic data are available on the expression of adipokines leptin (LEP) and adiponectin (ADIPOQ) and adipokine receptors (LEPR, ADIPOR1, ADIPOR2) in the breast tumor microenvironment (TME). The associations of gene expression of these biomarkers with tumor clinicopathology are not well understood. Methods: NanoString multiplexed assays were used to assess the gene expression levels of LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 within tumor tissues among 162 Black and 55 White women with newly diagnosed breast cancer. Multivariate mixed effects models were used to estimate associations of gene expression with breast tumor clinicopathology (overall and separately among Blacks). Results: Black race was associated with lower gene expression of LEPR (P = 0.002) and ADIPOR1 (P = 0.01). Lower LEP, LEPR, and ADIPOQ gene expression were associated with higher tumor grade (P = 0.0007, P < 0.0001, and P < 0.0001, respectively) and larger tumor size (P < 0.0001, P = 0.0005, and P < 0.0001, respectively). Lower ADIPOQ expression was associated with ER- status (P = 0.0005), and HER2-enriched (HER2-E; P = 0.0003) and triple-negative (TN; P = 0.002) subtypes. Lower ADIPOR2 expression was associated with Ki67+ status (P = 0.0002), ER- status (P < 0.0001), PR- status (P < 0.0001), and TN subtype (P = 0.0002). Associations of lower adipokine and adipokine receptor gene expression with ER-, HER2-E, and TN subtypes were confirmed using data from The Cancer Genome Atlas (P-values < 0.005). Conclusion: These findings suggest that lower expression of ADIPOQ, ADIPOR2, LEP, and LEPR in the breast TME might be indicators of more aggressive breast cancer phenotypes. Validation of these findings are warranted to elucidate the role of the adipokines and adipokine receptors in long-term breast cancer prognosis.

Original languageEnglish (US)
Pages (from-to)785-798
Number of pages14
JournalBreast Cancer Research and Treatment
Volume185
Issue number3
DOIs
StatePublished - Feb 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Adiponectin
  • Adiponectin receptors 1 and 2
  • Aggressive breast tumor features
  • Breast tumor microenvironment
  • Gene expression
  • Leptin
  • Leptin receptor

Fingerprint

Dive into the research topics of 'Gene expression of adipokines and adipokine receptors in the tumor microenvironment: associations of lower expression with more aggressive breast tumor features'. Together they form a unique fingerprint.

Cite this