Pharmacogenomics and Personalized Medicine (Dec 2020)
A Seven-NF-κB-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma
Abstract
Chao-Yi Ge,1,* Li-Yuan Wei,2,* Yu Tian,1 Hua-Hong Wang1 1Department of Gastroenterology, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Breast Surgery, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua-Hong WangDepartment of Gastroenterology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of ChinaTel +86 010- 83575675Email [email protected]: Ulcerative colitis (UC) patients have an increased risk of colorectal cancer (CRC), and compared with sporadic CRC, ulcerative colitis-associated colorectal cancer (CAC) is more aggressive with a worse prognosis. This study aimed to identify a gene signature to predict the risk of CAC for patients with UC in remission.Patients and Methods: Series of quiescent UC-related transcriptome data obtained from the Gene Expression Omnibus (GEO) data set were divided into a training set and a validation set. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and \Weighted Correlation Network Analysis (WGCNA) combined with protein–protein interaction (PPI) analysis were used to identify the pathways and gene signatures related to tumorigenesis among quiescent UC patients. A generalized linear model (GLM) of Poisson regression based on the training set was applied to estimate the diagnostic power of the gene signature in our validation set.Results: The tumor necrosis factor (TNF) signaling via NF-κB pathway was significantly augmented with the highest normalized enrichment score (NES). The genes in the brown module from WGCNA have shown a significant correlation with CAC (Pearson coefficient = 0.83, p = 6e-06). A subset of NF-κB related genes (FOS, CCL4, CXCL1, MYC, CEBPB, ATF3, and JUNB) were identified with a relatively higher expression level in CAC samples. The diagnostic value of this 7-gene biomarker was estimated by the receiver operating characteristic (ROC) curve with an area under the ROC curve (AUC) at 0.82 (p< 0.0001, 95% CI: 0.7098– 0.9400) in the validation cohort.Conclusion: In summary, the increased expression of this seven-NF-κB-related gene signature may act as a powerful index for tumorigenesis prediction among patients with UC in remission.Keywords: ulcerative colitis; UC, remission, colitis-associated colorectal cancer; CAC, diagnostic model
