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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....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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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. |
format | Online Article Text |
id | pubmed-8410141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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