Transcriptional expression of radiation-induced early cortical morphological alterations and its association with radiation necrosis in patients with nasopharyngeal carcinoma

Abstract

Purpose: To explore the effects of standard radiotherapy on cortical morphology and its potential transcriptional expression, and to determine the predictive power of cortical morphological measurement at the early stage for radiation necrosis (RN) occurrence within 3 years post-radiotherapy in patients with nasopharyngeal carcinoma (NPC).

Methods: 185 NPC patients participated. Pre-treatment and post-radiotherapy (1-3 months) structural MRI were collected longitudinally and prospectively. Multiple cortical morphological indices were compared between pre-treatment and post-radiotherapy. Brain-wide gene expression was used to assess the transcriptional profiles associated with radiation-induced cortical morphological changes. Machine learning was used to construct predictive models for RN with cortical morphological alterations at the early stage.

Results: Relative to pre-treatment, NPC patients exhibited a widespread reduction in cortical volume (CV) and cortical thickness (CT) post-radiotherapy (p < 0.001). Partial least squares regression analysis revealed that radiotherapy-related cortical atrophy was closely related to transcriptional profiles (p < 0.001), with the most correlated genes enriched in ATPase Na⁺/K⁺ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Furthermore, models constructed with cortical morphological features at 1-3 months post-radiotherapy had favorable predictive power for RN occurrence in NPC patients within 3-year follow-up, the area under the curve was 0.854 and 0.843 for CV and CT, respectively.

Conclusions: NPC patients exhibited widespread cortical atrophy at 1-3 months post-radiotherapy, which was closely correlated with dysfunction of the ATPase Na⁺/K⁺ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Cortical morphology at 1-3 months post-radiotherapy may serve as an early biomarker for identifying RN.

Keywords: Cortical morphology; Gene expression profiles; Nasopharyngeal carcinoma; Radiation necrosis; Radiotherapy.