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

Frank A. Sinicrope, Qian Shi, Thomas C. Smyrk, Richard M. Goldberg, Steven J. Cohen, Sharlene Gill, Morton S. Kahlenberg, Suresh Nair, Anthony F. Shield, Balkrishna N. Jahagirdar, Sawyer B. Jacobson, Nathan R. Foster, Michael N. Pollak, Steven R. Alberts

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numberpkab070
JournalJNCI Cancer Spectrum
Issue number5
StatePublished - Oct 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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