Zheng Xuan, Li Feng, Zhao Hongying, Tang Yongjuan, Xue Ke, Zhang Xiaomeng, Liang Weixin, Zhao Rui, Lv Xingyu, Song Xinyu, Zhang Chunlong, Xu Yanjun, Zhang Yunpeng
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Comput Struct Biotechnol J. 2023 Mar 24;21:2471-2482. doi: 10.1016/j.csbj.2023.03.041. eCollection 2023.
Cancer is a highly heterogeneous disease, and different individuals of the same cancer type can display different therapeutic effects and prognosis. Genetic variation of long non-coding RNA is the key factor driving tumor development, and plays an important role in genetic and biological heterogeneity. Therefore, it is of great significance to identify lncRNA as a driving factor in the non-coding region and explain its function in tumors for revealing the pathogenesis of cancer. In this study, we developed an integrated method to identify Personalized Functional Driver lncRNAs (PFD-lncRNAs) by integrating the DNA copy number data, gene expression data, and the biological subpathways information. Then, we applied the method to identify 2695 PFD-lncRNAs in 5334 samples across 19 cancer types. We performed an analysis of the association between PFD-lncRNAs and drug sensitivity, which provides medication guidance in disease therapy and drug discovery in the individual. Our research is of great significance for elucidating the biological roles of lncRNA genetic variation in cancer, revealing the related mechanism of cancer, and providing novel insights for individualized medicine.
癌症是一种高度异质性疾病，同一癌症类型的不同个体可能表现出不同的治疗效果和预后。长链非编码RNA的基因变异是驱动肿瘤发展的关键因素，在遗传和生物学异质性中起重要作用。因此，将lncRNA鉴定为非编码区的驱动因素并解释其在肿瘤中的功能对于揭示癌症的发病机制具有重要意义。在本研究中，我们开发了一种综合方法，通过整合DNA拷贝数数据、基因表达数据和生物子通路信息来鉴定个性化功能驱动lncRNA（PFD-lncRNA）。然后，我们应用该方法在19种癌症类型的5334个样本中鉴定出2695个PFD-lncRNA。我们对PFD-lncRNA与药物敏感性之间的关联进行了分析，这为个体疾病治疗和药物发现提供了用药指导。我们的研究对于阐明lncRNA基因变异在癌症中的生物学作用、揭示癌症相关机制以及为个性化医疗提供新见解具有重要意义。
