口腔白斑病光动力治疗中氧化应激相关生长调控分子的疗效预判价值与机制研究

项目组发现,口腔白斑病(OLK)的光动力治疗(PDT)中约有40%患者出现治疗抵抗；而如何根据OLK发病分子机制研究,寻找精准的疗效预判标志物,是学科的前沿。因此,结合项目组OLK发病机制研究、大数据分析取得的成果,项目组假设,针对氧化应激相关生长调控分子的多组学研究,能鉴定出OLK的PDT敏感与抵抗的分子标志。为此,拟:①进一步建立与完善OLK的PDT多中心临床队列;②通过计算生物学整合临床与多组学的数据(单细胞转录组测序、质谱流式蛋白组技术、氧化应激指标),鉴定出PDT敏感与抵抗的分子标志,并评估其疗效预判价值;③以细胞、动物模型,多层次、多角度探讨疗效预判标志分子导致PDT抵抗的生物学基础;④针对疗效预判标志分子抵抗机制,提出增强疗效的新策略。项目不仅有助于鉴定出OLK的PDT疗效预判标志物,阐明相关的发病机制,改善临床疗效,同时,也有利于保持和提升四川省口腔黏膜病学领域的创新水平。

Molecular typing was conducted for OLK patients based on the efficacy of PDT, to explore the predictive value and mechanism of molecular typing markers in OLK on the efficacy of PDT. Based on the mechanism of molecular typing markers resisting PDT treatment, new photosensitizers or PDT combined targeted drugs were developed, and molecular diagnosis and accurate treatment of OLK were preliminarily realized. The research content involves four parts: first, the enrichment and improvement of the initial queue and the multi-center verification queue in chengdu center; Secondly, the tissue/blood samples in the initial cohort were analyzed for single-cell transcriptome /CyTOF proteome/oxidative stress. The molecular typing markers based on the efficacy of PDT were identified by integrating clinical and multi-group data from computational biology, and the validation cohort was used to obtain the molecular typing markers based on the efficacy of OKL PDT. Then, multi-level biological techniques were used to analyze the mechanism of molecular typing markers affecting the efficacy of PDT. Finally, novel or coassembled photosensitizers with specific reduction and elimination factors were developed to analyze the molecular mechanism of typing markers, and strategies for enhancing the efficacy of PDT were sought. To form a new individualized PDT therapy strategy based on OLK molecular typing.