Frontiers in Genetics (May 2022)
Identification of Context-Specific Fitness Genes Associated With Metabolic Rearrangements for Prognosis and Potential Treatment Targets for Liver Cancer
- Shizhe Yu,
- Shizhe Yu,
- Shizhe Yu,
- Haoren Wang,
- Jie Gao,
- Jie Gao,
- Jie Gao,
- Long Liu,
- Long Liu,
- Long Liu,
- Xiaoyan Sun,
- Xiaoyan Sun,
- Xiaoyan Sun,
- Zhihui Wang,
- Zhihui Wang,
- Zhihui Wang,
- Peihao Wen,
- Peihao Wen,
- Peihao Wen,
- Xiaoyi Shi,
- Xiaoyi Shi,
- Xiaoyi Shi,
- Jihua Shi,
- Jihua Shi,
- Jihua Shi,
- Wenzhi Guo,
- Wenzhi Guo,
- Wenzhi Guo,
- Shuijun Zhang,
- Shuijun Zhang,
- Shuijun Zhang
Affiliations
- Shizhe Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Shizhe Yu
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Shizhe Yu
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Haoren Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jie Gao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jie Gao
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Jie Gao
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Long Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Long Liu
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Long Liu
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Xiaoyan Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Xiaoyan Sun
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Xiaoyan Sun
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Zhihui Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhihui Wang
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Zhihui Wang
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Peihao Wen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Peihao Wen
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Peihao Wen
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Xiaoyi Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Xiaoyi Shi
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Xiaoyi Shi
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Jihua Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jihua Shi
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Jihua Shi
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Wenzhi Guo
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Wenzhi Guo
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Shuijun Zhang
- Henan Engineering Technology Research Center for Organ Transplantation, Zhengzhou, China
- Shuijun Zhang
- Zhengzhou Engineering Laboratory for Organ Transplantation Technique and Application, Zhengzhou, China
- DOI
- https://doi.org/10.3389/fgene.2022.863536
- Journal volume & issue
-
Vol. 13
Abstract
Liver cancer is the most frequent fatal malignancy. Furthermore, there is a lack of effective therapeutics for this cancer type. To construct a prognostic model for potential beneficiary screens and identify novel treatment targets, we used an adaptive daisy model (ADaM) to identify context-specific fitness genes from the CRISPR-Cas9 screens database, DepMap. Functional analysis and prognostic significance were assessed using data from TCGA and ICGC cohorts, while drug sensitivity analysis was performed using data from the Liver Cancer Model Repository (LIMORE). Finally, a 25-gene prognostic model was established. Patients were then divided into high- and low-risk groups; the high-risk group had a higher stemness index and shorter overall survival time than the low-risk group. The C-index, time-dependent ROC curves, and multivariate Cox regression analysis confirmed the excellent prognostic ability of this model. Functional enrichment analysis revealed the importance of metabolic rearrangements and serine/threonine kinase activity, which could be targeted by trametinib and is the key pathway in regulating liver cancer cell viability. In conclusion, the present study provides a prognostic model for patients with liver cancer and might help in the exploration of novel therapeutic targets to ultimately improve patient outcomes.
Keywords
- liver cancer
- molecular targeted therapy
- CRISPR-Cas9 screens
- fitness genes
- drug sensitivity
- metabolism
