Li Lin, Feng Qiushi, Wang Xiaosheng
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Comput Struct Biotechnol J. 2020 Mar 19;18:668-675. doi: 10.1016/j.csbj.2020.03.007. eCollection 2020.
Microsatellite instability (MSI) is a genomic property of the cancers with defective DNA mismatch repair and is a useful marker for cancer diagnosis and treatment in diverse cancer types. In particular, MSI has been associated with the active immune checkpoint blockade therapy response in cancer. Most of computational methods for predicting MSI are based on DNA sequencing data and a few are based on mRNA expression data. Using the RNA-Seq pan-cancer datasets for three cancer cohorts (colon, gastric, and endometrial cancers) from The Cancer Genome Atlas (TCGA) program, we developed an algorithm (PreMSIm) for predicting MSI from the expression profiling of a 15-gene panel in cancer. We demonstrated that PreMSIm had high prediction performance in predicting MSI in most cases using both RNA-Seq and microarray gene expression datasets. Moreover, PreMSIm displayed superior or comparable performance versus other DNA or mRNA-based methods. We conclude that PreMSIm has the potential to provide an alternative approach for identifying MSI in cancer.
微卫星不稳定性（MSI）是DNA错配修复缺陷型癌症的一种基因组特性，是多种癌症类型中癌症诊断和治疗的有用标志物。特别是，MSI与癌症中活跃的免疫检查点阻断治疗反应相关。大多数预测MSI的计算方法基于DNA测序数据，少数基于mRNA表达数据。利用来自癌症基因组图谱（TCGA）项目的三个癌症队列（结肠癌、胃癌和子宫内膜癌）的RNA测序泛癌数据集，我们开发了一种算法（PreMSIm），用于从癌症中15个基因的表达谱预测MSI。我们证明，在大多数情况下，使用RNA测序和微阵列基因表达数据集，PreMSIm在预测MSI方面具有很高的预测性能。此外，与其他基于DNA或mRNA的方法相比，PreMSIm表现出优越或相当的性能。我们得出结论，PreMSIm有可能为识别癌症中的MSI提供一种替代方法。
