Abstract
BackgroundThe immune infiltration of patients with colon cancer (CC) is closely associated with RNA-binding proteins (RBPs). However, immune-associated RBPs (IARBPs) in CC remain unexplored.MethodsThe data were downloaded from The Cancer Genome Atlas (TCGA) and the patients were divided into four immune subgroups by single sample gene set enrichment analysis (ssGSEA), in which weighted gene correlation network analysis (WGCNA) identified modules of co-expressed genes correlated with immune infiltration. Univariate (UCR) and multivariate Cox regression (MCR) analyses were applied to screen survival-associated IARBPs. Then, a prognostic signature was performed on TCGA dataset. Risk model was constructed based on the TCGA dataset. Based on the median risk score, CC patients were subdivided into low- and high-risk groups. Furthermore, the accuracy and prognostic value of this signature were validated by using Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC). We further validated the findings in Gene Expression Omnibus (GEO) database. Finally, we evaluated the association between gene expression level and drug sensitivity.ResultsBased on the infiltration of immune cells, the TCGA patients were divided into four subgroups. In total, we identified 25 IARBPs, after differential expression and WGCNA analysis. Subsequently, two IARBP signatures (FBXO17 and PPARGC1A) were identified to be significantly associated with the overall survival (OS) of CC patients. K-M survival analysis revealed that the low-risk group correlated with prolonged OS. The prognostic signature was an independent prognostic factor and reflects the immune status of CC patients. Finally, FBXO17 was related with drug sensitivity of bleomycin, gemcitabine, and lenvatinib. PPARGC1A was related to drug sensitivity of dabrafenib, vemurafenib, and trametinib.ConclusionA novel two immune-associated RBPs that was established that may be useful in predicting survival and individualized treatment.
Highlights
Colon cancer (CC), one of the most common digestive malignant tumors, has become an important public health issue
We evaluated the association between the expression of immune-associated RNA-binding proteins (RBPs) (IARBPs) and prognosis in CC patients
Identification of CC subtypes based on ssGSEA score and differentially expressed genes identification For each CC dataset, 27 immune cell types were determined using the single sample gene set enrichment analysis software implemented in the R GSVA package
Summary
Colon cancer (CC), one of the most common digestive malignant tumors, has become an important public health issue. The effective prediction model can play a significant role for the accurate assessment of patients’ prognosis and to optimize clinical treatment strategies [6,7,8,9,10]. A growing number of evidences indicate that the potential effect of the tumor immune microenvironment (TIM) have great potential for predicting the efficacy of immunotherapy as well as prognosis [11]. Adaptive anti-tumor immune responses have been correlated with tumor progression in various cancers, including CC, and tumor development is dependent on the infiltration of immune cells [12]. The immune infiltration of patients with colon cancer (CC) is closely associated with RNA-binding proteins (RBPs).
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