TY - JOUR
T1 - Association of Adiponectin and Vitamin D with Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
AU - Sinicrope, Frank A.
AU - Shi, Qian
AU - Smyrk, Thomas C.
AU - Goldberg, Richard M.
AU - Cohen, Steven J.
AU - Gill, Sharlene
AU - Kahlenberg, Morton S.
AU - Nair, Suresh
AU - Shield, Anthony F.
AU - Jahagirdar, Balkrishna N.
AU - Jacobson, Sawyer B.
AU - Foster, Nathan R.
AU - Pollak, Michael N.
AU - Alberts, Steven R.
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jncics/pkab070
DO - 10.1093/jncics/pkab070
M3 - Article
C2 - 34485815
AN - SCOPUS:85118122579
SN - 2515-5091
VL - 5
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
IS - 5
M1 - pkab070
ER -