Development of a 5-mRNAsi-related gene signature to predict the prognosis of colon adenocarcinoma

AIM: To create a prognosis model based on mRNA-based stem index (mRNAsi) for evaluating the prognostic outcomes of colon adenocarcinoma (COAD). BACKGROUND: Generation of heterogeneous COAD cells could be promoted by the self-renewal and differentiation potential of cancer stem cells (CSCs). Biomarkers contributing to the development of COAD stem cells remained to be discovered. OBJECTIVE: To develop and validate an mRNAsi-based risk model for estimating the prognostic outcomes of patients suffering from COAD. METHODS: Samples were collected from Rectal Adenocarcinoma (TCGA-READ) PanCancer Atlas datasets, The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD), and the GSE87211 dataset. MRNAsi was calculated by one-class logistic regression (OCLR) algorithm. Under the criterion of correlation greater than 0.4, genes related to mRNAsi were screened and clustered. Meanwhile, differentially expressed genes (DEGs) between molecular subtypes were identified to establish a risk model. According to the median risk score value for immunotherapy and results from immune cell infiltration and clinicopathological analyses, clusters and patients were divided into high-RiskScore and low-RiskScore groups. Cell apoptosis and viability were detected by flow cytometer and Cell Counting Kit-8 (CCK-8) assay, respectively. RESULTS: A negative correlation between mRNAsi and clinical stages was observed. Three clusters of patients (C1, C2, and C3) were defined based on a total of 165 survival-related mRNAsi genes. Specifically, C1 patients had greater immune cell infiltration and a poorer prognosis. A 5-mRNAsi-gene signature (HEYL, FSTL3, FABP4, ADAM8, and EBF4) served as a prediction index for COAD prognosis. High-RiskScore patients had a poorer prognosis and higher level of immune cell infiltration. In addition, the five genes in the signature all showed a high expression in COAD cells. Knocking down HEYL promoted COAD cell apoptosis and inhibited viability. CONCLUSION: Our mRNAsi risk model could better predict the prognosis of COAD patients.