Longitudinal Analysis of Soluble Vitamin D, Homocysteine, PD-L1, and PD-1 in Colorectal Cancer
Mühl Dorottya
Pathological Sciences
Dr. Matolcsy András
Országos Onkológiai Intézet
2025-11-11 11:00:00
Experimental Oncology
Dr. Bödör Csaba
Dr. Dank Magdolna
Dr. Kovács Árpád
Dr. Nagy Zsolt
Dr. Tamás László
Dr. Furka Andrea
Dr. Bánky Balázs
Background: Vitamin D, homocysteine, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) are known to play a role in the pathophysiology of colorectal cancer (CRC). However, little is known about their combined and longitudinal effect in CRC.
Methods: The serum vitamin D and the homocysteine level of 86 CRC patients was measured in a longitudinal observational study. Plasma PD-1 and PD-L1 levels were measured in a subset of the original cohort, in 37 metastatic CRC (mCRC) patients.
Results: The 86 CRC patients were enrolled into four cohorts based on the presence of metastases (Adj vs. Met) and vitamin D supplementation (ND vs. D). Vitamin D was constant (Adj-ND), increased significantly (Adj-D, p = 0.0261), decreased (Met-ND), or returned close to the baseline after an initial increase (Met-D). Its longitudinal increase positively affected the overall survival in non-metastatic CRC, however, this effect was cancelled out in those with metastasis (p = 0.0107). The longitudinal change in homocysteine had a swoosh-shaped trend and it negatively affected both the overall (HR: 1.0940, p = 0.0067) and the progression-free survival (HR: 1.0845, p = 0.0073). No statistically justifiable connection was found between the two target variables.
Disease progression (p = 0.0443) and baseline high-sensitivity C-reactive protein (p = 0.0011), aspartate transaminase (p = 0.0253), alanine transaminase (p = 0.0386), and gamma-glutamyl transferase (p = 0.0103) were associated with higher PD-L1 levels. Disease-specific survival and progression-free survival were significantly shorter in patients with high PD-L1.
Based on the baseline PD-1/PD-L1 levels, low and high PD-1/PD-L1 groups were created. Constant, pathological levels of complete blood count values, high-sensitivity C-reactive protein, serum albumin, high-density lipoprotein cholesterol, and lactate dehydrogenase were characteristic for patients with high baseline PD-L1. High PD-L1 levels were significantly associated with increased tumor burden.
Conclusions: Abnormal levels of laboratory parameters and intensified tumor burden can be expected if elevated baseline plasma PD-1/PD-L1 levels are found. A measurement-based titration of vitamin D supplementation, and a more complex oncology that is more dependent on interdisciplinary solutions is recommended for CRC.
