4.7 Article

Identification of important genes and drug repurposing based on clinical-centered analysis across human cancers

期刊

ACTA PHARMACOLOGICA SINICA
卷 42, 期 2, 页码 282-289

出版社

NATURE PUBL GROUP
DOI: 10.1038/s41401-020-0451-1

关键词

clinical correlation; survival outcomes; somatic mutation; drug repurposing; network analysis; pancancer

资金

  1. National Natural Science Foundation of China [81602620, 81502086, 81572896, 8172203, 91859205]
  2. National Major Scientific and Technological Special Project for Significant New Drugs Development [2018ZX09101-002]
  3. Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning [20154Y0140]
  4. Shanghai Pujiang Program [18PJD060]

向作者/读者索取更多资源

Identifying the functional impact of mutated and altered genes in cancer is crucial for precision oncology and drug repurposing. Through multidimensional analysis of multiomics data, it was found that survival-associated genes differ in their position in biological networks and enrich in different pathways, providing important insights for gene identification and drug development.
Identification of the functional impact of mutated and altered genes in cancer is critical for implementing precision oncology and drug repurposing. In recent years, the emergence of multiomics data from large, well-characterized patient cohorts has provided us with an unprecedented opportunity to address this problem. In this study, we investigated survival-associated genes across 26 cancer types and found that these genes tended to be hub genes and had higher K-core values in biological networks. Moreover, the genes associated with adverse outcomes were mainly enriched in pathways related to genetic information processing and cellular processes, while the genes with favorable outcomes were enriched in metabolism and immune regulation pathways. We proposed using the number of survival-related neighbors to assess the impact of mutations. In addition, by integrating other databases including the Human Protein Atlas and the DrugBank database, we predicted novel targets and anticancer drugs using the drug repurposing strategy. Our results illustrated the significance of multidimensional analysis of clinical data in important gene identification and drug development.

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