The underlying molecular mechanisms and prognostic factors of RNA binding protein in colorectal cancer: a study based on multiple online databases

Abstract

Background RNA binding protein (RBP) is an active factor involved in the occurrence and development of colorectal cancer (CRC). Therefore, the potential mechanism of RBP in CRC needs to be clarified by dry-lab analyses or wet-lab experiments. Methods The differential RBP gene obtained from the GEPIA 2 (Gene Expression Profiling Interactive Analysis 2) were performed functional enrichment analysis. Then, the alternative splicing (AS) events related to survival were acquired by univariate regression analysis, and the correlation between RBP and AS was analyzed by R software. The online databases were conducted to analyze the mutation and methylation of RBPs in CRC. Moreover, 5 key RBP signatures were obtained through univariate and multivariate Cox regression analysis and established as RBP prognosis model. Subsequently, the above model was verified through another randomized group of TCGA CRC cohorts. Finally, multiple online databases and qRT-PCR analysis were carried to further confirm the expression of the above 5 RBP signatures in CRC. Results Through a comprehensive bioinformatics analysis, it was revealed that RBPs had genetic and epigenetic changes in CRC. We obtained 300 differentially expressed RBPs in CRC samples. The functional analysis suggested that they mainly participated in spliceosome. Then, a regulatory network for RBP was established to participate in AS and DDX39B was detected to act as a potentially essential factor in the regulation of AS in CRC. Our analysis discovered that 11 differentially expressed RBPs with a mutation frequency higher than 5%. Furthermore, we found that 10 differentially expressed RBPs had methylation sites related to the prognosis of CRC, and a prognostic model was constructed by the 5 RBP signatures. In another randomized group of TCGA CRC cohorts, the prognostic performance of the 5 RBP signatures was verified. Conclusion The potential mechanisms that regulate the aberrant expression of RBPs in the development of CRC was explored, a network that regulated AS was established, and the RBP-related prognosis model was constructed and verified, which could improve the individualized prognosis prediction of CRC.

Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3β Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay

“…Moreover, BRCC3 was involved in BC cell proliferation and invasion by binding to TRAF1, thus influencing the activation of the NF-κB pathway [ 33 ]. In addition, the analysis from the TCGA database revealed that the mutated or aberrant expression of RBPs was closely related to the prognosis in patients with BC [ 34 ]. Our previous study revealed that RBM5, as an important RBP member, was downregulated in BC tissues and cells [ 9 ].…”

Adaptation of Graph Convolutional Neural Networks and Graph Layer-wise Relevance Propagation to the Spektral library with application to gene expression data of Colorectal Cancer patients

“…The computed topmost occurrences using the STRING network show, that selected genes, e.g. CAPRIN2 or TM9SF2, are linked to the survival of colorectal cancer patients (He et al ., 2021; Clark et al ., 2018). The Spektral implementations also selected multiple genes related to colorectal cancer, e.g.…”

Development and Validation of an 8-Gene Signature to Improve Survival Prediction of Colorectal Cancer

“…Time-dependent area under the curve (AUC) values were employed to compare the predictive accuracy of clinical predictors and the risk signature. Moreover, receiver operating characteristic (ROC) curves were used to compare the predictive ability of our signature with nine recently published prognostic signatures for CRC patients ( 20 – 28 ).…”