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

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....

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Autores principales: Sinicrope, Frank A, Shi, Qian, Smyrk, Thomas C, Goldberg, Richard M, Cohen, Steven J, Gill, Sharlene, Kahlenberg, Morton S, Nair, Suresh, Shield, Anthony F, Jahagirdar, Balkrishna N, Jacobson, Sawyer B, Foster, Nathan R, Pollak, Michael N, Alberts, Steven R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410141/
https://www.ncbi.nlm.nih.gov/pubmed/34485815
http://dx.doi.org/10.1093/jncics/pkab070
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author Sinicrope, Frank A
Shi, Qian
Smyrk, Thomas C
Goldberg, Richard M
Cohen, Steven J
Gill, Sharlene
Kahlenberg, Morton S
Nair, Suresh
Shield, Anthony F
Jahagirdar, Balkrishna N
Jacobson, Sawyer B
Foster, Nathan R
Pollak, Michael N
Alberts, Steven R
author_facet Sinicrope, Frank A
Shi, Qian
Smyrk, Thomas C
Goldberg, Richard M
Cohen, Steven J
Gill, Sharlene
Kahlenberg, Morton S
Nair, Suresh
Shield, Anthony F
Jahagirdar, Balkrishna N
Jacobson, Sawyer B
Foster, Nathan R
Pollak, Michael N
Alberts, Steven R
author_sort Sinicrope, Frank A
collection PubMed
description 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/m(2)) 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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spelling pubmed-84101412021-09-02 Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer Sinicrope, Frank A Shi, Qian Smyrk, Thomas C Goldberg, Richard M Cohen, Steven J Gill, Sharlene Kahlenberg, Morton S Nair, Suresh Shield, Anthony F Jahagirdar, Balkrishna N Jacobson, Sawyer B Foster, Nathan R Pollak, Michael N Alberts, Steven R JNCI Cancer Spectr Article 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/m(2)) 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. Oxford University Press 2021-07-23 /pmc/articles/PMC8410141/ /pubmed/34485815 http://dx.doi.org/10.1093/jncics/pkab070 Text en © The Author(s) 2021. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Sinicrope, Frank A
Shi, Qian
Smyrk, Thomas C
Goldberg, Richard M
Cohen, Steven J
Gill, Sharlene
Kahlenberg, Morton S
Nair, Suresh
Shield, Anthony F
Jahagirdar, Balkrishna N
Jacobson, Sawyer B
Foster, Nathan R
Pollak, Michael N
Alberts, Steven R
Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
title Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
title_full Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
title_fullStr Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
title_full_unstemmed Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
title_short Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer
title_sort association of adiponectin and vitamin d with tumor infiltrating lymphocytes and survival in stage iii colon cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410141/
https://www.ncbi.nlm.nih.gov/pubmed/34485815
http://dx.doi.org/10.1093/jncics/pkab070
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