Modulation Effects of the CEP128 Gene on Radiotherapy-Related Brain Injury: A Longitudinal Structural Study Using Multi-Parametric Brain MR Images.

ABSTRACT

BACKGROUND: The promoter variant rs17111237 in the CEP128 closely relates to radiotherapy (RT)-related brain necrosis in nasopharyngeal carcinoma (NPC) patients. PURPOSE: To explore RT-related dynamic alterations in brain morphology and their potential genetic mechanism, and to explore the modulatory effects of CEP128 genetic variants on RT-related brain morphological alterations in NPC patients. STUDY TYPE Prospective, longitudinal. POPULATION One hundred one patients with histopathologic ally-proven NPC (age 41.64 ± 9.63, 46 male), analyzed at baseline (pre-RT), 3-months post-RT and 6 months post-RT, and 19 sex-, age- and education-matched healthy controls. FIELD STRENGTH/SEQUENCE 3D gradient echo brain volume (3D-BRAVO) and diffusion-weighted single-shot spin-echo echo-planar sequences at 3.0 T. ASSESSMENT rs17111237 in CEP128 was detected by Sanger sequencing. Structural and diffusion images were processed with FreeSurfer and FSL. Morphometric similarity network (MSN) was constructed with nine cortical indices derived from structural and diffusion images. STATISTICAL TESTS One-way ANOVA, chi-square test. Pearson's correlation analysis was conducted to measure the relationship between CEP128 gene-expression level in human brain and MSN alterations. Repeated analysis of variance performed to assess group differences in MSN and the modulatory effects of the CEP128 gene within patients. Significance level P < 0.05, false-discovery rate correction. RESULTS: RT-related significant widespread MSN alterations were observed in the cortices of NPC patients. Notably, regional MSN alterations had a weak but significant negative correlation with the cortical pattern of CEP128 gene expression (r = -0.152). Furthermore, rs17111237 in the CEP128 had significant modulatory effects on the observed MSN alterations in NPC patients, with the modulatory effects being most obvious at 3 months post-RT. CONCLUSIONS: MSN has potential to serve as a sensitive biomarker to detect RT-related brain injury. Inter-brain regional and inter-patient variability of RT-related brain injuries may be attributed to the cortical expression of the CEP128 gene and the modulatory effects of the promoter variant rs17111237 in CEP128. EVIDENCE LEVEL 2 TECHNICAL EFFICACY Stage 2.