TY - JOUR TI - Gene interaction perturbation network deciphers a high-resolution taxonomy in colorectal cancer AU - Liu, Zaoqu AU - Weng, Siyuan AU - Dang, Qin AU - Xu, Hui AU - Ren, Yuqing AU - Guo, Chunguang AU - Xing, Zhe AU - Sun, Zhenqiang AU - Han, Xinwei A2 - Lou, Emil A2 - El-Deiry, Wafik S A2 - Sun, Ruping VL - 11 PY - 2022 DA - 2022/11/08 SP - e81114 C1 - eLife 2022;11:e81114 DO - 10.7554/eLife.81114 UR - https://doi.org/10.7554/eLife.81114 AB - Molecular subtypes of colorectal cancer (CRC) are currently identified via the snapshot transcriptional profiles, largely ignoring the dynamic changes of gene expressions. Conversely, biological networks remain relatively stable irrespective of time and condition. Here, we introduce an individual-specific gene interaction perturbation network-based (GIN) approach and identify six GIN subtypes (GINS1-6) with distinguishing features: (i) GINS1 (proliferative, 24%~34%), elevated proliferative activity, high tumor purity, immune-desert, PIK3CA mutations, and immunotherapeutic resistance; (ii) GINS2 (stromal-rich, 14%~22%), abundant fibroblasts, immune-suppressed, stem-cell-like, SMAD4 mutations, unfavorable prognosis, high potential of recurrence and metastasis, immunotherapeutic resistance, and sensitive to fluorouracil-based chemotherapy; (iii) GINS3 (KRAS-inactivated, 13%~20%), high tumor purity, immune-desert, activation of EGFR and ephrin receptors, chromosomal instability (CIN), fewer KRAS mutations, SMOC1 methylation, immunotherapeutic resistance, and sensitive to cetuximab and bevacizumab; (iv) GINS4 (mixed, 10%~19%), moderate level of stromal and immune activities, transit-amplifying-like, and TMEM106A methylation; (v) GINS5 (immune-activated, 12%~24%), stronger immune activation, plentiful tumor mutation and neoantigen burden, microsatellite instability and high CpG island methylator phenotype, BRAF mutations, favorable prognosis, and sensitive to immunotherapy and PARP inhibitors; (vi) GINS6, (metabolic, 5%~8%), accumulated fatty acids, enterocyte-like, and BMP activity. Overall, the novel high-resolution taxonomy derived from an interactome perspective could facilitate more effective management of CRC patients. KW - biological network KW - gene interaction KW - colorectal cancer KW - molecular subtype KW - precision medicine JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -