Abstract
BackgroundRNA 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.MethodsThe 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.ResultsThrough 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.ConclusionThe 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.
Highlights
RNA binding protein (RBP) is an active factor involved in the occurrence and development of colorectal cancer (CRC)
Differential expression analysis and functional enrichment analysis The abnormally expressed genes in CRC samples were collected on the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database, of which 300 RBP genes were differentially expressed in CRC (Additional file 2)
Expressed RBPs in CRC and their enrichment network We acquired an exhaustive list of 1542 RBPs from the literature published by Gerstberger et al (Additional file 1)
Summary
RNA binding protein (RBP) is an active factor involved in the occurrence and development of colorectal cancer (CRC). Despite some improvements in diagnosis and treatment, global mortality He et al Cancer Cell Int (2021) 21:325 remains high [1]. Many studies often showed that there is a lack of significant correlation between transcripts and protein levels in cells [7] These observations lead the public to believe that other processes may play an important role in the cell pool that affects the translation of proteins from their respective transcripts. This paradox can be further explained by identifying post-transcriptional regulatory points, which make a great contribution to the regulation of protein level. These checkpoints are mainly composed of regulation mediated by non-coding RNAs (microRNAs, circular RNAs and long non-coding RNAs) and RNA-binding proteins (RBPs) [8, 9]
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