Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer

JNCI Cancer Spectr. 2021 Jul 23;5(5):pkab070. doi: 10.1093/jncics/pkab070. eCollection 2021 Oct.

Abstract

Background: Adipocyte-derived adiponectin may play a role in the host inflammatory response to cancer. We examined the association of plasma adiponectin with the density of tumor-infiltrating lymphocytes (TILs) in colon cancers and with vitamin D, clinicopathological features, and patient survival.

Methods: Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon cancer who received FOLFOX-based adjuvant chemotherapy (NCCTG N0147 [Alliance]). TIL densities were determined in histopathological sections. Associations with disease-free survival (DFS), time to recurrence, and overall survival were evaluated by multivariable Cox regression adjusting for potential confounders (ie, body mass index, race, TILs, and N stage). All statistical tests were 2-sided.

Results: We found a statistically significant reduction in adiponectin, but not 25(OH)D, levels in tumors with high vs low TIL densities (median = 6845 vs 8984 ng/mL; P = .04). A statistically significant reduction in adiponectin was also observed in obese (body mass index >30 kg/m2) vs nonobese patients (median = 6608 vs 12 351 ng/mL; P < .001), in men vs women (median = 8185 vs 11 567 ng/mL; P < .001), in Blacks vs Whites or Asians (median = 6412 vs 8847 vs 7858 ng/mL; P < .03), and in those with fewer lymph node metastases (N1 vs N2: median = 7768 vs 9253 ng/mL; P = .01). Insufficiency of 25(OH)D (<30 ng/mL) was detected in 291 (48.5%) patients. In multivariable analyses, neither adiponectin nor 25(OH)D were associated with a statistically significant difference in DFS, overall survival , or time to recurrence in models adjusted for potential confounders. We found a statistically significant association of TILs with prognosis, yet no such interaction was observed for the association of adiponectin with TILs for DFS.

Conclusions: Lower circulating adiponectin levels were associated with a statistically significant increase in TIL densities in colon cancers, indicating an enhanced antitumor immune response. In contrast to TILs, neither adiponectin nor 25(OH)D was independently prognostic.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood*
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Body Mass Index
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / blood
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Lymphatic Metastasis
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Organoplatinum Compounds / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Racial Groups
  • Sex Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • Adiponectin
  • Organoplatinum Compounds
  • Vitamin D
  • 25-hydroxyvitamin D
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol