Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning
Özet
Clear cell renal cell carcinoma (ccRCC) is the most common histological type of kidney cancer and has high heterogeneity. Stratification of ccRCC is important since distinct subtypes differ in prognosis and treatment. Here, we applied a systems biology approach to stratify ccRCC into three molecular subtypes with different mRNA expression patterns and prognosis of patients. Further, we developed a set of biomarkers that could robustly classify the patients into each of the three subtypes and predict the prognosis of patients. Then, we reconstructed subtype-specific metabolic models and performed essential gene analysis to identify the potential drug targets. We identified four drug targets, including SOAT1, CRLS1, and ACACB, essential in all the three subtypes and GPD2, exclusively essential to subtype 1. Finally, we repositioned mitotane, an FDA-approved SOAT1 inhibitor, to treat ccRCC and showed that it decreased tumor cell viability and inhibited tumor cell growth based on in vitro experiments.
Sürdürülebilir Kalkınma Amaçları
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SKA 3: Sağlıklı Bireyler
Atıf için künye
Li, X., Kim, W., Juszczak, K., Arif, M., Sato, Y., Kume, H., Ogawa, S., Türkez, H., Boren, J., Nielsen, J., Uhlen, M., Zhang, C., & Mardinoglu, A. (2021). Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning. ISCIENCE, 24(7). https://doi.org/10.1016/j.isci.2021.102722
BibTeX
@article{li2021-245022,
author = {Li, Xiangyu and Kim, Woonghee and Juszczak, Kajetan and Arif, Muhammad and Sato, Yusuke and Kume, Haruki and Ogawa, Seishi and Türkez, Hasan and Boren, Jan and Nielsen, Jens and Uhlen, Mathias and Zhang, Cheng and Mardinoglu, Adil},
title = {Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning},
journal = {ISCIENCE},
year = {2021},
volume = {24},
number = {7},
issn = {2589-0042},
doi = {10.1016/j.isci.2021.102722},
url = {https://akademik.atauni.edu.tr/yayinlar/245022-stratification-of-patients-with-clear-cell-renal-cell-carcinoma-to-facilitate}
}