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

Abstract

BackgroundThe promoter variant rs17111237 in the CEP128 closely relates to radiotherapy (RT)‐related brain necrosis in nasopharyngeal carcinoma (NPC) patients.PurposeTo 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 TypeProspective, longitudinal.PopulationOne 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/Sequence3D gradient echo brain volume (3D‐BRAVO) and diffusion‐weighted single‐shot spin‐echo echo‐planar sequences at 3.0 T.Assessmentrs17111237 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 TestsOne‐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.ResultsRT‐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.ConclusionsMSN 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 Level2Technical EfficacyStage 2

Heterogeneity of morphometric similarity networks in health and schizophrenia

“…The reduced morphometric similarity in the group of individuals with chronic schizophrenia aligns with previous research morphometric similarity findings as well as general default mode dysfunction in high-risk, early-onset and chronic schizophrenia (Morgan et al, 2019; Whitfield-Gabrieli et al, 2009; Yao et al, 2023). A recent study demonstrated that morphometric similarity was positively correlated with the likelihood of cellular network structures forming axonal connections (Lin et al, 2024). In schizophrenia, axonal dysconnectivity between networks might lead to the micro-structural and functional connectivity deficits observed across various age groups affected by the disease, including children, adolescents, and adults (Barth et al, 2023; Heuvel and Sporns, 2019; Kelly et al, 2018).…”

Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns

“…EOS1 exhibited differences in MSN strength in multiple functional and von Economo atlas, whereas EOS2 displayed abnormalities only in MSN strength within motor networks. Previous studies have demonstrated that high/low MSN strength implies that the cellular structures of similar/differentiated networks could be more/less likely to form axonal connections to each other [ 41 ]. Changes in the brain develop rapidly from childhood to adolescence as myelination and synapse pruning [ 42 , 43 ].…”

Editorial for “Modulation Effects of the CEP128 Gene on Radiotherapy‐Related Brain Injury: A Longitudinal Structural Study Using Multi‐Parametric Brain MR Images”

“…In this issue of JMRI, an article by Lin et al 7 applies MSN to a cohort of 101 patients with NPC treated with radiotherapy in a well‐designed longitudinal study design and shows that there are detectable changes in the mean MSN at 3‐ and 6‐month post radiotherapy. The MSN abnormalities involved the bilateral temporal and frontal lobes as well as left occipital lobe and left parietal lobe.…”

“…Beyond the important impact in treatment of NPC, patients with non‐NPC malignancies such as brain metastases or high‐grade gliomas, would also potentially benefit. While it remains to be seen if MSN or similar computational methods will be incorporated into the imaging of patients undergoing radiation therapy, or if treatments based on the biology of CEP128 will be developed, the work by Lin et al 7 takes us an important step further toward those goals.…”