Abstract
Abnormal expression of RNA binding proteins (RBPs) has been reported across various cancers. However, the potential role of RBPs in colorectal cancer (CRC) remains unclear. In this study, we performed a systematic bioinformatics analysis of RBPs in CRC. We downloaded CRC data from The Cancer Genome Atlas (TCGA) database. Our analysis identified 242 differentially expressed RBPs between tumor and normal tissues, including 200 upregulated and 42 downregulated RBPs. Next, we found eight RBPs (RRS1, PABPC1L, TERT, SMAD6, UPF3B, RP9, NOL3, and PTRH1) related to the prognoses of CRC patients. Among these eight prognosis-related RBPs, four RBPs (NOL3, PTRH1, UPF3B, and SMAD6) were selected to construct a prognostic risk score model. Furthermore, our results indicated that the prognostic risk score model accurately predicted the prognosis of CRC patients [area under the receiver operating characteristic curve (AUC)for 3- and 5-year overall survival (OS) and was 0.645 and 0.672, respectively]. Furthermore, we developed a nomogram based on a prognostic risk score model. The nomogram was able to demonstrate the wonderful performance in predicting 3- and 5-year OS. Additionally, we validated the clinical value of four risk genes in the prognostic risk score model and identified that these risk genes were associated with tumorigenesis, lymph node metastasis, distant metastasis, clinical stage, and prognosis. Finally, we used the TIMER and Human Protein Atlas (HPA)database to validate the expression of four risk genes at the transcriptional and translational levels, respectively, and used a clinical cohort to validate the roles of NOL3 and UPF3B in predicting the prognosis of CRC patients. In summary, our study demonstrated that RBPs have an effect on CRC tumor progression and might be potential prognostic biomarkers for CRC patients.
Highlights
Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract
The R package Limma was used to identify differentially expressed RNA binding proteins (RBPs) according to the following parameters: | log2FC| > 1 and false discovery rate (FDR) < 0.05
We validated the clinical value of the four risk genes and found that they were associated with tumorigenesis, lymph node metastasis, distant metastasis, clinical stage, and overall survival (OS)
Summary
Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract. It is the third leading cause of cancer-related death worldwide (Siegel et al, 2020). RNA binding proteins (RBPs) are a class of proteins involved in splicing, modifications, transport, localization, stability, degradation, and translation of RNAs (Mitchell and Parker, 2014; Perron et al, 2018). Expressed RBPs regulate the expression and function of oncogenes and tumor-suppressor genes via post-transcriptional regulatory mechanisms across various cancers. CPEB4 increased the translation of melanoma drivers MITF and RAB72A, which helps promote tumor proliferation (Pérez-Guijarro et al, 2016). HuR/methyl-HuR and AUF1 modulate MAT1A and MAT2A expression through posttranslational regulation of their messenger RNAs (mRNAs), impacting tumor progression (Vázquez-Chantada et al, 2010). In CRC, overexpression of IMP-1 increased proliferation by directly binding to and stabilizing c-Myc (Mongroo et al, 2011)
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