Abstract
BackgroundEpithelial 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.MethodsWe 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.ResultsThree 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.ConclusionsThis 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.
Highlights
Epithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness
Heterogeneity of clinical process and treatment response are often observed between individuals in the same stage, which are often attributed to diversity of CRC [4]
We used GSE39582 as training set to identified prognostic gene. 98 genes (DNA repair: 41; EMT: 57) were eventually identified and defined as prognostic EMT and DNA repair genes for further study
Summary
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. Heterogeneity of clinical process and treatment response are often observed between individuals in the same stage, which are often attributed to diversity of CRC [4]. Tumors of the same histological subtype may have different genetic backgrounds and gene expression profile. Tumors of different histological subtype may share common genetic backgrounds and molecular features. Identifying tumor subtypes with different molecular characteristics and clinical outcome is important for the precise treatment of cancer
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