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The Plasma Levels and Polymorphisms of Vitronectin Predict Radiation Pneumonitis in Patients With Lung Cancer Receiving Thoracic Radiation Therapy

Jia-Hua Yu, Qing-Ya Zhao, Yuan Liu, Xue-Ru Zhu, Zhang-Ru Yang, Xiao-Long Fu,

Abstract: Purpose Our previous findings have identified vitronectin (VTN) as a potential biomarker for radiation pneumonitis (RP) through proteomics and molecular mechanism studies. In a recent study, we further explored associations of plasma level and single nucleotide polymorphisms of VTN with the risk of RP in patients with lung cancer receiving radiation therapy. Methods and Materials A total of 165 patients with lung cancer were prospectively enrolled with detection of VTN concentration before radiation therapy. VTN reference single nucleotide polymorphisms, rs704 and rs2227721, were genotyped by Taqman probe method. Cox proportional hazard models were performed to identify clinical variables and genotypes associated with the risk of RP on univariate and multivariate analyses, and t tests and analysis of variance were conducted to evaluate the expression level of VTN. Results The baseline secretion level of VTN in patients with grade ≥3 RP was significantly higher than that in grade <3 RP patients (P< .0001), and elevated levels were observed in patients having the AA genotype compared with GA/GG genotypes of rs704. The VTN rs704 GA/GG and rs2227721 AA/AC genotypes had a significantly lower risk of RP (hazard ratio [HR], 0.448, P = .005; HR, 0.419, P = .008, respectively). In addition, combining cut-off values of mean lung dose (MLD) and VTN plasma level, grade ≥3 RP risk groupings were as follows: high risk: MLD ≥12 Gy and VTN level ≥132 μg/mL (RP rate, 10 of 16 patients, 62.5%); intermediate risk: MLD ≥12 Gy and VTN level <132 μg/mL or MLD <12 Gy and VTN level ≥132 μg/mL (8 of 70 patients, 11.4%); and low risk: MLD <12 Gy and VTN level <132 μg/mL (1 of 79 patients, 1.3%) (P< .0001). Conclusions Among patients receiving radiation therapy, relatively high plasma levels of VTN before radiation therapy were associated with the higher incidence of RP, and VTN rs704 and rs2227721 each had a significant effect on predicting RP risk. Combining VTN concentration with MLD appeared to facilitate stratification of patients with lung cancer who received radiation therapy into low-, intermediate-, and high-risk RP groups. This study indicated that VTN may serve as a blood biomarker for susceptibility to RP in patients with lung cancer.
Keywords: VTN concentration / receiving radiation therapy / μg/mL / VTN rs704 / rs704 and rs2227721

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