Chang Zhiqiang, Liu Xinxin, Zhao Wenyuan, Xu Yan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Mol Ther Methods Clin Dev. 2020 Jun 24;18:501-510. doi: 10.1016/j.omtm.2020.06.020. eCollection 2020 Sep 11.
Dosage effect is one of the common mechanisms of somatic copy number alteration in the development of colorectal cancer, yet the roles of dosage-sensitive genes (DSGs) in colorectal cancer (CRC) remain to be characterized more deeply. In this study, we developed a five-step pipeline to identify DSGs and analyzed their characterization in CRC. Results showed that our pipeline performed better than existing methods, and the result was significantly overlapped between solid tumor and cell line. We also found that the top five DSGs (, and ) were associated with the progression of CRC. By analyzing the characterization, DSGs were enriched in driver genes and they drove sub-pathways of CRC. In addition, immune-related DSGs are associated with CRC progression. Our results also showed that the CRC samples affected by high microsatellites have fewer DSGs, but a higher overlap with DSGs in microsatellite low instability and microsatellite stable samples. In addition, we applied DSGs to identify potential drug targets, with the results showing that 22 amplified DSGs were more sensitive to four drugs. In conclusion, DSGs play an important role in CRC, and our pipeline is effective to identify them.
剂量效应是结直肠癌发生过程中体细胞拷贝数改变的常见机制之一，但剂量敏感基因（DSGs）在结直肠癌（CRC）中的作用仍有待更深入地研究。在本研究中，我们开发了一个五步流程来识别DSGs，并分析它们在CRC中的特征。结果表明，我们的流程比现有方法表现更好，并且实体瘤和细胞系之间的结果有显著重叠。我们还发现，排名前五的DSGs（……）与CRC的进展相关。通过分析其特征，DSGs在驱动基因中富集，并且驱动了CRC的子通路。此外，免疫相关的DSGs与CRC进展相关。我们的结果还表明，受高微卫星影响的CRC样本中DSGs较少，但与微卫星低不稳定性和微卫星稳定样本中的DSGs有更高的重叠。此外，我们应用DSGs来识别潜在的药物靶点，结果显示22个扩增的DSGs对四种药物更敏感。总之，DSGs在CRC中起重要作用，并且我们的流程能有效地识别它们。
