Xiaoliang Huang1,2, Jungang Liu1,2,3, Haizhou Liu4, Xianwei Mo1,2, Yongsheng Meng1,2, Lihua Zhang1,2, Yuqing Deng1,2, Yawei Zhang3, Weizhong Tang1,2. 1. Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China. 2. Guangxi Clinical Research Center for Colorectal Cancer, Nanning, China. 3. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, United States. 4. Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China.
Abstract
BACKGROUND: Epithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness. We sought to develop a combined EMT and DNA repair gene panel with potential application in patient classification and precise treatment. METHODS: We comprehensively evaluated the EMT and DNA repair patterns of 1,652 CRC patients from four datasets. Unsupervised clustering was used for classification. The clinical features, genetic mutation, tumor mutation load, and chemotherapy as well as immunotherapy sensitivity among different clusters were systematically compared. The least absolute shrinkage and selection operator regression method was used to develop the risk model. RESULTS: Three distinct CRC clusters were determined. Clustet1 was characterized by down-regulated DNA repair pathways but active epithelial markers and metabolism pathway and had intermediate prognosis. Clustet2 was characterized by down-regulated both epithelial markers and DNA repair pathways and had poor outcome. Clustet3 presented with activation of DNA repair pathway and epithelial markers had favorable prognosis. Clustet1 might benefit form chemotherapy and Clustet3 had a higher response rate to immunotherapy. An EMT and DNA repair risk model related to prognosis and treatment response was developed. CONCLUSIONS: This work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.
BACKGROUND: Epithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness. We sought to develop a combined EMT and DNA repair gene panel with potential application in patient classification and precise treatment. METHODS: We comprehensively evaluated the EMT and DNA repair patterns of 1,652 CRC patients from four datasets. Unsupervised clustering was used for classification. The clinical features, genetic mutation, tumor mutation load, and chemotherapy as well as immunotherapy sensitivity among different clusters were systematically compared. The least absolute shrinkage and selection operator regression method was used to develop the risk model. RESULTS: Three distinct CRC clusters were determined. Clustet1 was characterized by down-regulated DNA repair pathways but active epithelial markers and metabolism pathway and had intermediate prognosis. Clustet2 was characterized by down-regulated both epithelial markers and DNA repair pathways and had poor outcome. Clustet3 presented with activation of DNA repair pathway and epithelial markers had favorable prognosis. Clustet1 might benefit form chemotherapy and Clustet3 had a higher response rate to immunotherapy. An EMT and DNA repair risk model related to prognosis and treatment response was developed. CONCLUSIONS: This work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.
Authors: Neal W Wilkinson; Greg Yothers; Samia Lopa; Joseph P Costantino; Nicholas J Petrelli; Norman Wolmark Journal: Ann Surg Oncol Date: 2010-04 Impact factor: 5.344
Authors: Rick Kamps; Rita D Brandão; Bianca J van den Bosch; Aimee D C Paulussen; Sofia Xanthoulea; Marinus J Blok; Andrea Romano Journal: Int J Mol Sci Date: 2017-01-31 Impact factor: 5.923
Authors: Therese Sorlie; Robert Tibshirani; Joel Parker; Trevor Hastie; J S Marron; Andrew Nobel; Shibing Deng; Hilde Johnsen; Robert Pesich; Stephanie Geisler; Janos Demeter; Charles M Perou; Per E Lønning; Patrick O Brown; Anne-Lise Børresen-Dale; David Botstein Journal: Proc Natl Acad Sci U S A Date: 2003-06-26 Impact factor: 12.779