College of Life Science, Shanghai University, Shanghai, 200444, People' Republic of China.
College of Information Engineering, Shanghai Maritime University, Shanghai, 201306, People's Republic of China.
Int J Cancer. 2018 Oct 1;143(7):1731-1740. doi: 10.1002/ijc.31554. Epub 2018 May 10.
Colorectal cancer is the third most common cancer in males and second in females. This disease can be caused by genetic and acquired/environmental factors. Microsatellite instability (MSI) is one of the major mechanisms in colorectal cancer. This mechanism is a specific condition of genetic hyper mutability that results from incompetent DNA mismatch repair. MSI has been applied to classify different colorectal cancer subtypes. However, the effects of MSI status on gene expression are largely unknown. In our study, we integrated the gene expression profile and MSI status of all CRC samples from the TCGA database, and then categorized the CRC samples into three subgroups, namely, MSI-stable, MSI-low, and MSI-high, according to the MSI status. We applied a novel computational method based on machine learning and screened the genes specifically expressed for the different colorectal cancer subtypes. The results showed the distinct mechanisms of the different colorectal cancer subtypes with MSI status and provided the genes that may be the optimal standards to further classify the various molecular subtypes of colorectal cancer with distinct MSI status.
结直肠癌是男性中第三常见的癌症，在女性中则是第二常见的癌症。这种疾病可能由遗传和后天/环境因素引起。微卫星不稳定性 (MSI) 是结直肠癌的主要机制之一。这种机制是由于 DNA 错配修复功能不全导致的遗传高突变的特定情况。MSI 已被应用于对不同的结直肠癌亚型进行分类。然而，MSI 状态对基因表达的影响在很大程度上是未知的。在我们的研究中，我们整合了来自 TCGA 数据库的所有 CRC 样本的基因表达谱和 MSI 状态，然后根据 MSI 状态将 CRC 样本分为 MSI 稳定型、MSI 低型和 MSI 高型三个亚组。我们应用了一种基于机器学习的新计算方法，筛选出针对不同结直肠癌亚型特异性表达的基因。结果表明，不同 MSI 状态下结直肠癌亚型具有不同的机制，并提供了可能是进一步对具有不同 MSI 状态的各种分子亚型的结直肠癌进行分类的最佳标准的基因。
