Abstract
The prognosis of colon adenocarcinoma (COAD) remains poor. However, the specific and sensitive biomarkers for diagnosis and prognosis of COAD are absent. Transcription factors (TFs) are involved in many biological processes in cells. As the molecule of the signal pathway of the terminal effectors, TFs play important roles in tumorigenesis and development. A growing body of research suggests that aberrant TFs contribute to the development of COAD, as well as to its clinicopathological features and prognosis. In consequence, a few studies have investigated the relationship between the TF-related risk model and the prognosis of COAD. Therefore, in this article, we hope to develop a prognostic risk model based on TFs to predict the prognosis of patients with COAD. The mRNA transcription data and corresponding clinical data were downloaded from TCGA and GEO. Then, 141 differentially expressed genes, validated by the GEPIA2 database, were identified by differential expression analysis between normal and tumor samples. Univariate, multivariate and Lasso Cox regression analysis were performed to identify seven prognostic genes (E2F3, ETS2, HLF, HSF4, KLF4, MEIS2, and TCF7L1). The Kaplan–Meier curve and the receiver operating characteristic curve (ROC, 1-year AUC: 0.723, 3-year AUC: 0.775, 5-year AUC: 0.786) showed that our model could be used to predict the prognosis of patients with COAD. Multivariate Cox analysis also reported that the risk model is an independent prognostic factor of COAD. The external cohort (GSE17536 and GSE39582) was used to validate our risk model, which indicated that our risk model may be a reliable predictive model for COAD patients. Finally, based on the model and the clinicopathological factors, we constructed a nomogram with a C-index of 0.802. In conclusion, we emphasize the clinical significance of TFs in COAD and construct a prognostic model of TFs, which could provide a novel and reliable model for the prognosis of COAD.
Highlights
Colon cancer is one of the most common malignant tumors and the fifth leading cause of cancerrelated death worldwide (Bray et al, 2018)
Recent studies mainly focused on the predicting value of Transcription factors (TFs)-related genes; the present study constructed an original risk score model based on TF-related genes with remarkable predicting efficiency in colon adenocarcinoma (COAD) patients
Gene expression data and clinical data of COAD patients were downloaded from The Cancer Genome Atlas (TCGA) database
Summary
Colon cancer is one of the most common malignant tumors and the fifth leading cause of cancerrelated death worldwide (Bray et al, 2018). The significant differences in survival outcomes of COAD patients with the same clinicopathologic characteristics still exist, which signifies that a prognostic model based solely on clinicopathologic characteristics is of limited value (Nagtegaal et al, 2011; Bruni et al, 2020; Wang T. et al, 2020). Several significant TFs, such as nuclear factor κB (NF-κB) and cAMPresponse element-binding protein (CREB), have been found that aberrantly express in COAD and promote the development of COAD (Rayet & Gelinas, 1999; Hui et al, 2014). TFs may be important biomarkers for predicting prognosis, as well as potential targets for the treatment of COAD patients. Recent studies mainly focused on the predicting value of TF-related genes; the present study constructed an original risk score model based on TF-related genes with remarkable predicting efficiency in COAD patients
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