Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer

J Surg Oncol. 2018 Jun;117(8):1833-1840. doi: 10.1002/jso.25078. Epub 2018 May 14.

Abstract

Background: Obesity is closely associated with colorectal cancer (CRC), but the underlying mechanism is unclear. We thus evaluated the expression of the adipokine gene family in CRC tissues and its clinicopathological implications.

Methods: Correlations between the mRNA expression levels of the adipokine gene family (ADIPOQ, ADIPOR1/2, LEP, LEPR, RETN, RETNLB, RBP4, SFRP5, NAMPT, and SPP1) in CRC tissue and clinicopathologic factors were analyzed using data from The Cancer Genome Atlas database.

Results: Tissue samples from 369 patients were analyzed, and 82 deaths occurred during follow-up (median, 670 days). Overall, mortality was associated with positive venous invasion, higher TNM stage, and increased ADIPOR1 (adiponectin receptor 1 gene) and SPP1 (secreted phosphoprotein gene 1) mRNA expression. Higher ADIPOR1 (odds ratio [OR]: 3.29, 95% confidence interval [CI]: 1.33-8.13) and SPP1 (OR: 2.31, 95%CI: 1.49-3.59) levels were independently associated with increased mortality. A Kaplan-Meier survival analysis showed shorter overall survival times in patients with higher ADIPOR1 (P = 0.006) and SPP1 (P < 0.001) expression.

Conclusions: Upregulation of ADIPOR1 and SPP1, among the adipokine gene family, in cancer tissue is associated with poor survival in CRC, suggesting a potential mechanism linking obesity and CRC. ADIPOR1 and SPP1 expression could become useful prognostic indicators after further validation.

Keywords: TCGA data; adipokine; colorectal cancer; obesity; prognosis.

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism*
  • Survival Analysis
  • Up-Regulation*

Substances

  • ADIPOR1 protein, human
  • Biomarkers
  • RNA, Messenger
  • Receptors, Adiponectin
  • SPP1 protein, human
  • Osteopontin