A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma

Abstract

BackgroundColon adenocarcinoma (COAD) is a fatal disease, and its cases are constantly increasing worldwide. Further, the therapeutic and management strategies for patients with COAD are still unsatisfactory due to the lack of accurate patient classification and prognostic models. Therefore, our study aims to identify prognostic markers in patients with COAD and construct a cell subtype-specific prognostic model with high accuracy and robustness.MethodsSingle-cell transcriptomic data of six samples were retrieved from the Gene expression omnibus (GEO) database. The cluster annotation and cell-cell communication analysis identified enterocytes as a key player mediating signal communication networks. A four-gene signature prognostic model was constructed based on the enterocyte-related differentially expressed genes (ERDEGs) in patients with COAD of the Cancer Genome Atlas cohort. The prognostic model was validated on three external validation cohorts from the GEO database. The correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the four-gene signature prognostic model was investigated. Finally, immunohistochemistry (IHC) was performed to determine the expression of the four genes.ResultsWe found that the proportion of epithelial cells was obviously large in COAD samples. Further analysis of epithelial cells showed that the activity of the enterocytes was highest in the cell-cell communication network. Based on enterocyte data, 30 ERDEGs were identified and a 4-gene prognostic model including CPM, CLCA4, ELOVL6, and ATP2A3 was developed and validated. The risk score derived from this model was considered as an independent variable factor to predict overall survival. The patients were divided into high- and low-risk groups based on the median riskscore value. The correlation between immune cell infiltration, immunotherapy response, immune status, clinical characteristics, drug sensitivity, and risk score was analyzed. IHC confirmed the expression of signature genes in tissues from normal individuals, patients with polyps, and COAD.ConclusionIn this study, we constructed and validated a novel four-gene signature prognostic model, which could effectively predict the response to immunotherapy and overall survival in patients with COAD. More importantly, this model provides useful insight into the management of colon cancer patients and aids in designing personalized therapy.

The anoikis-related gene signature predicts survival accurately in colon adenocarcinoma

“…Furthermore, SERCA3 expression is lower in adenocarcinomas 58 . These results suggest a strong correlation between transition from adenomatous polyposis to adenocarcinoma, COAD development, and aberrant SERCA3 expression 59 . Previous studies have shown that these model genes are related to the occurrence and progression of most tumors, which is consistent with our research results.…”

Qi Lang formula relieves constipation via targeting SCF/c-kit signaling pathway: An integrated study of network pharmacology and experimental validation

“…After manual merging and annotation, we ultimately presented 10 unique cell clusters ( Fig. 3 A) [ 23 , 24 ]. Then, we annotated the clusters based on several canonical marker genes for known cell lineages: T cell (CD3D, CD3E), ICC (ANO1), smooth muscle (MYH11), lymphatic endothelial cell (CCL21), glial cell (S100B), PDGFRA + cell (PDGFRA), macrophages (CD14), mast cell (TPSAB1, TPSB2), Vessel endothelial cell (VWF) and unknow ( Fig.…”

Current Targeted Therapy for Metastatic Colorectal Cancer

“…Although the latest therapeutic strategies have achieved substantial progress in patients with mCRC, emerging resistance and lack of predictive biomarkers to current targeted therapies remains a major problem in clinical settings. Further understanding of resistance mechanisms and exploration of biomarkers that can predict the treatment sensitivity and efficacy/toxicity are required to test new evidence-based therapeutic strategies, expand treatment options, and realize personalized medicine [ 145 , 146 , 147 , 148 ].…”