Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China; School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China; Corresponding author
Chunyu Pan
School of Computer Science and Engineering, Northeastern University, Shenyang, China
Xinru Wei
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China; School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
Meng Yu
Department of Laboratory Animal Science, China Medical University, Shenyang, China; Key Laboratory of Transgenetic Animal Research, China Medical University, Shenyang, China
Shuangjie Liu
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, China
Jun An
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, China
Jieping Yang
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, China
Baojun Wei
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, China
Wenjun Hao
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, China
Yang Yao
Department of Physiology, Shenyang Medical College, Shenyang, China; Corresponding author
Yuyan Zhu
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, China; Corresponding author
Weixiong Zhang
Department of Health Technology and Informatics, Department of Computing, The Hong Kong Polytechnic University, Hong Kong, China; Department of Computer Science and Engineering, Department of Genetics, Washington University in St. Louis, St. Louis, MO, USA; Corresponding author
Summary: Finding cancer-driver genes has been a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth, which we named cancer-keeper genes (CKGs). Intervening CKGs may rectify aberrant cell growth, making them potential cancer therapeutic targets. We introduced control-hub genes and developed an efficient algorithm by extending network controllability theory. Control hub are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA). All genes on the cell-cycle and p53 pathways in BLCA were identified as CKGs, showing their importance in cancer. We discovered that sensitive CKGs — genes easily altered by structural perturbation — were particularly suitable therapeutic targets. Experiments on cell lines and a mouse model confirmed that six sensitive CKGs effectively suppressed cancer cell growth, demonstrating the immense therapeutic potential of CKGs.
