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Total, bioavailable and free 25-hydroxyvitamin D are associated with the prognosis of patients with non-small cell lung cancer



To analyze the prognostic value of total, bioavailable and free 25-hydroxyvitamin D [25(OH)D] as well as vitamin D-binding protein (VDBP) in patients with non-small cell lung cancer (NSCLC).


We prospectively collected and analyzed data for 395 patients diagnosed with NSCLC between January 2016 and December 2018 in two university-affiliated hospitals. Total and free 25(OH)D and VDBP were measured directly, and bioavailable 25(OH)D was calculated using a validated formula. Their prognostic values were evaluated by Cox proportional hazards model, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.


Patients with NSCLC had significantly lower levels of total, bioavailable, and free 25(OH)D and higher VDBP levels in comparison to healthy controls (all p < 0.001). In multivariate analyses, higher levels of total, bioavailable, and free 25(OH)D were independently associated better overall survival (OS) and progression-free survival (PFS). For OS, the adjusted HRs were 0.58 (95% CI, 0.40–0.87; p for trend = 0.008), 0.45 (95% CI, 0.30–0.67; p for trend < 0.001) and 0.49 (95% CI, 0.33–0.73; p for trend < 0.001) for the highest versus the lowest tertile of total, bioavailable and free 25(OH)D, respectively. The corresponding adjusted HRs for PFS were 0.61 (95% CI, 0.43–0.86; p for trend = 0.006), 0.56 (95% CI, 0.40–0.80; p for trend = 0.001) and 0.60 (95% CI, 0.42–0.85; p for trend = 0.004), respectively. However, VDBP was not associated with either OS or PFS.


The current study suggested that total, bioavailable and free 25(OH)D may be reliable prognosis indicators in NSCLC patients, though the optimal 25(OH)D form for NSCLC prognosis remains to be assessed in future studies.

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Data availability

All datasets generated for this manuscript can be obtained from the corresponding author on reasonable request.


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This work was supported by the project of State key laboratory of radiation medicine and protection (GZK1202007); the second affiliate hospital of Soochow university science and technology innovation team project funding (XKTJ-TD202009); and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Correspondence to Yu-Song Zhang or Li-Qiang Qin.

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This study was approved by the Research Ethics Committee of Soochow University (Approval No. ESCU-2015-0002). All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Peng, SM., Yu, N., Che, J. et al. Total, bioavailable and free 25-hydroxyvitamin D are associated with the prognosis of patients with non-small cell lung cancer. Cancer Causes Control 33, 983–993 (2022).

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