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鼻咽癌患者放射诱导早期皮质形态改变的转录表达及其与放射性坏死的关系。

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

机构信息

Department of Radiology, Huazhong University of Science and Technology Union Shenzhen Hospital, 89 Taoyuan road, Nanshan district, Shenzhen 518052, China.

Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen 518055, China.

出版信息

Radiother Oncol. 2023 Sep;186:109770. doi: 10.1016/j.radonc.2023.109770. Epub 2023 Jun 28.

DOI:10.1016/j.radonc.2023.109770
PMID:37385380
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.

摘要

目的

探索标准放疗对皮质形态的影响及其潜在的转录表达,并确定鼻咽癌(NPC)患者放疗后 3 年内皮质形态测量对放射性坏死(RN)发生的早期预测能力。

方法

共纳入 185 名 NPC 患者。前瞻性地采集了患者治疗前和放疗后(1-3 个月)的结构 MRI。比较了治疗前和放疗后皮质形态学的多项指标。利用全脑基因表达来评估与放射诱导皮质形态变化相关的转录谱。利用机器学习构建早期皮质形态改变预测 RN 的模型。

结果

与治疗前相比,NPC 患者放疗后皮质体积(CV)和皮质厚度(CT)广泛下降(p<0.001)。偏最小二乘回归分析显示,放疗相关的皮质萎缩与转录谱密切相关(p<0.001),最相关的基因富集于 Na/K 转运体α-1 和α-3 多肽和呼吸电子传递链相关基因。此外,构建的基于放疗后 1-3 个月皮质形态特征的模型对 NPC 患者 3 年内 RN 发生具有良好的预测能力,CV 和 CT 的曲线下面积分别为 0.854 和 0.843。

结论

NPC 患者在放疗后 1-3 个月出现广泛的皮质萎缩,与 Na/K 转运体α-1 和α-3 多肽和呼吸电子传递链功能障碍密切相关。放疗后 1-3 个月的皮质形态学可作为识别 RN 的早期生物标志物。

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