Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial
Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of...
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| Online Access: | https://www.mdpi.com/2072-6643/13/6/1987 |
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| author | Makoto Morita Mai Okuyama Taisuke Akutsu Hironori Ohdaira Yutaka Suzuki Mitsuyoshi Urashima |
| author_facet | Makoto Morita Mai Okuyama Taisuke Akutsu Hironori Ohdaira Yutaka Suzuki Mitsuyoshi Urashima |
| author_sort | Makoto Morita |
| collection | DOAJ |
| description | Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1–Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (<i>p</i> = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (<i>p</i> = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2–Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12–0.92) and relapse/death (HR, 0.37; 95% CI, 0.15–0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (P<sub>interaction</sub> = 0.02 for death, P<sub>interaction</sub> = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1. |
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| spelling | doaj.art-3bd7983773d846a1a97540a58762c1862023-11-21T23:26:32ZengMDPI AGNutrients2072-66432021-06-01136198710.3390/nu13061987Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled TrialMakoto Morita0Mai Okuyama1Taisuke Akutsu2Hironori Ohdaira3Yutaka Suzuki4Mitsuyoshi Urashima5Division of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo 105-8461, JapanDivision of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo 105-8461, JapanDivision of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo 105-8461, JapanDepartment of Surgery, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi 329-2763, JapanDepartment of Surgery, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi 329-2763, JapanDivision of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo 105-8461, JapanBecause vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1–Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (<i>p</i> = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (<i>p</i> = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2–Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12–0.92) and relapse/death (HR, 0.37; 95% CI, 0.15–0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (P<sub>interaction</sub> = 0.02 for death, P<sub>interaction</sub> = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1.https://www.mdpi.com/2072-6643/13/6/1987vitamin DsupplementPD-L1cancerserumsoluble |
| spellingShingle | Makoto Morita Mai Okuyama Taisuke Akutsu Hironori Ohdaira Yutaka Suzuki Mitsuyoshi Urashima Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial Nutrients vitamin D supplement PD-L1 cancer serum soluble |
| title | Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial |
| title_full | Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial |
| title_fullStr | Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial |
| title_full_unstemmed | Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial |
| title_short | Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial |
| title_sort | vitamin d supplementation regulates postoperative serum levels of pd l1 in patients with digestive tract cancer and improves survivals in the highest quintile of pd l1 a post hoc analysis of the amaterasu randomized controlled trial |
| topic | vitamin D supplement PD-L1 cancer serum soluble |
| url | https://www.mdpi.com/2072-6643/13/6/1987 |
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