期刊
JOURNAL OF CLINICAL MEDICINE
卷 7, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/jcm7100350
关键词
glioma; gene expression; Monte Carlo feature selection; Johnson reducer algorithm; support vector machine
资金
- National Natural Science Foundation of China [31701151]
- Natural Science Foundation of Shanghai [17ZR1412500]
- Shanghai Sailing Program
- Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) [2016245]
- fund of the key Laboratory of Stem Cell Biology of Chinese Academy of Sciences [201703]
- Science and Technology Commission of Shanghai Municipality (STCSM) [18dz2271000]
As a common brain cancer derived from glial cells, gliomas have three subtypes: glioblastoma, diffuse astrocytoma, and anaplastic astrocytoma. The subtypes have distinctive clinical features but are closely related to each other. A glioblastoma can be derived from the early stage of diffuse astrocytoma, which can be transformed into anaplastic astrocytoma. Due to the complexity of these dynamic processes, single-cell gene expression profiles are extremely helpful to understand what defines these subtypes. We analyzed the single-cell gene expression profiles of 5057 cells of anaplastic astrocytoma tissues, 261 cells of diffuse astrocytoma tissues, and 1023 cells of glioblastoma tissues with advanced machine learning methods. In detail, a powerful feature selection method, Monte Carlo feature selection (MCFS) method, was adopted to analyze the gene expression profiles of cells, resulting in a feature list. Then, the incremental feature selection (IFS) method was applied to the obtained feature list, with the help of support vector machine (SVM), to extract key features (genes) and construct an optimal SVM classifier. Several key biomarker genes, such as IGFBP2, IGF2BP3, PRDX1, NOV, NEFL, HOXA10, GNG12, SPRY4, and BCL11A, were identified. In addition, the underlying rules of classifying the three subtypes were produced by Johnson reducer algorithm. We found that in diffuse astrocytoma, PRDX1 is highly expressed, and in glioblastoma, the expression level of PRDX1 is low. These rules revealed the difference among the three subtypes, and how they are formed and transformed. These genes are not only biomarkers for glioma subtypes, but also drug targets that may switch the clinical features or even reverse the tumor progression.
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