Abstract
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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Acknowledgements
This study was funded by the National Natural Science Foundation of China (81602620, 81502086, 81572896, 8172203 and 91859205). National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09101-002), the Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning (No. 20154Y0140) and the Shanghai Pujiang Program (18PJD060).
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YL and YPD performed the centrality analysis, drafted and revised the manuscript. YWQ, LXY and WW participated in the statistical analysis and manuscript writing. XLC and HYW conceived and supervised this study.
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Li, Y., Dong, Yp., Qian, Yw. et al. Identification of important genes and drug repurposing based on clinical-centered analysis across human cancers. Acta Pharmacol Sin 42, 282–289 (2021). https://doi.org/10.1038/s41401-020-0451-1
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DOI: https://doi.org/10.1038/s41401-020-0451-1
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