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Gene dysregulation analysis builds a mechanistic signature for prognosis and therapeutic benefit in colorectal cancer

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Journal of Molecular Cell Biology 2020年第11期12卷 881-893页

作者： Quanxue Li Wentao Dai jixiang Liu Qingqing Sang Yi-Xue Li Yuan-Yuan Li School of Biotechnology East China University of Science and TechnologyShanghai 200237China Shanghai Center for Bioinformation Technology Shanghai 201203China Department of Surgery Shanghai Key Laboratory of Gastric NeoplasmsShanghai Institute of Digestive SurgeryRuijin HospitalShanghai jiao Tong University School of MedicineShanghai 200025China CAS Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Shanghai Engineering Research Center of Pharmaceutical Translation and Shanghai Industrial Technology Institute Shanghai 201203China

The implementation of cancer precision medicine requires biomarkers or signatures for predicting prognosis and therapeutic *** of current efforts in this field are paying much more attention to predictive accuracy than to molecular mechanistic ***-driven strategy has recently emerged,aiming to build signatures with both predictive power and explanatory *** by this strategy,we developed a robust gene dysregulation analysis framework with machine learning algorithms,which is capable of exploring gene dysregulations underlying carcinogenesis from high-dimensional data with cooperativity and synergy between regulators and several other transcriptional regulation rules taken into *** then applied the framework to a colorectal cancer(CRC)cohort from The Cancer Genome *** identified CRC-related dysregulations significantly covered known carcinogenic processes and exhibited good prognostic *** choosing dysregulations with greedy strategy,we built a four-dysregulation(4-DysReg)signature,which has the capability of predicting prognosis and adjuvant chemotherapy benefit.4-DysReg has the potential to explain carcinogenesis in terms of dysfunctional transcriptional *** results demonstrate that our gene dysregulation analysis framework could be used to develop predictive signature with mechanistic interpretability for cancer precision medicine,and furthermore,elucidate the mechanisms of carcinogenesis.

关键词： gene dysregulation analysis mechanistic signature cancer precision medicine prognosis chemotherapy benefit colorectal cancer

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