基于影像基因组学的鼻咽癌诱导化疗疗效预测模型及其机制研究

建立诱导化疗疗效预测模型对中晚期鼻咽癌个体化治疗十分重要，能提高疗效，避免过度治疗。我们前期建立了单纯基于影像组学的预测模型，可初步筛选诱导化疗获益人群，分析相关影像特征提示诱导化疗抵抗可能与肿瘤血管低灌注、缺氧有关。为进一步提高预测效能并明确化疗抵抗具体机制，我们分析比较了诱导化疗有无获益患者的治疗前基因表达水平，筛选出16个差异表达基因，其中ATMIN表达差异最显著，并与缺氧、化疗抵抗高度相关。预实验结果表明ATMIN可影响肿瘤血管生成，敲减ATMIN能增加鼻咽癌细胞化疗敏感性，提示ATMIN可能为影响诱导化疗疗效的重要基因。本项目拟在前期基础上，通过大样本进一步筛选与诱导化疗疗效有关的关键基因与影像特征，建立基于影像基因组学的疗效预测模型，指导中晚期鼻咽癌个体化治疗；通过体内外功能研究、分子生物学实验阐明ATMIN促进化疗抵抗的分子机制，为诱导化疗抵抗患者提供新的治疗靶点。

Establishing a model to predict efficacy of induction chemotherapy (IC) is the key to guide individualized treatment of advanced nasopharyngeal carcinoma (NPC). We developed a model based solely on radiomics, which could preliminarily screen the population with benefit from IC. Image traits suggested that resistance to IC may be attributed to blood hypoperfusion and hypoxia. In order to further improve the prediction efficiency and clarify the specific mechanism of chemoresistance, we analyzed and compared the pre-treatment gene expression level of patients with or without benefit of IC, and screened out 16 differentially expressed genes. Among them, the ATMIN expression was the most significant, and was highly correlated with hypoxia and chemoresistance. Preliminary experimental results showed that ATMIN could affect tumor angiogenesis, and ATMIN knockdown could sensitize NPC cells to chemotherapy, suggesting that ATMIN may be an important gene in affecting IC efficacy. This project aims to further screen the key genes and image features related to IC efficacy through large samples, and establish a prediction model based on radiogenomics to guide individualized treatment of advanced NPC. Besides, in vivo and in vitro functional studies and molecular biology experiments will be conducted to elucidate the molecular mechanism of ATMIN in promoting chemoresistance, so as to provide a new therapeutic target for patients resistant to IC.