Numerous studies have reported that the imbalance of the expression of RBPs leads to the progression of many cancers [16–18]. However, there are few research reports on the role of RBP in LUEC and its influence on tumor progression. In this study, we integrated LUEC's TCGA RNA and GSE17025 RNA sequencing data, and determined the differentially expressed RBP between cancer and normal tissues. We systematically studied related biological pathways and constructed PPIs for these RBPs. Then, the key RBP related to the prognosis was screened, and a risk model with 6 RBPs genes characteristics was constructed to predict the prognosis of LUEC.
In this study, GO biological process analysis found that the differentially expressed up-regulated RBPs were mainly concentrated in ncRNA metabolic process, mitochondrial matrix, catalytic activity, acting on RNA. The down-regulated RBPs were mainly concentrated on ribonucleoprotein granule, RNA splicing, catalytic activity, cytoplasmic ribonucleoprotein granule, acting on RNA. NcRNA has long been the focus of cancer research [19]. Abnormal regulation of ncRNA is related to the metastasis of many cancers [20]. RNA splicing is a very important biological process in the human body. RNA splicing can promote the growth and survival of cancer. Abnormal splicing is involved in the pathogenesis and pathogenesis of many cancers. Progress [21, 22]. KEGG enrichment analysis showed that abnormally expressed RBP was enriched in RNA transport, Ribosome and Spliceosome. Ribosomal biogenesis plays an important role in tumor genesis and progression. Ribosomal proteins affect tumor development by regulating the P53 pathway and mRNA translation[23, 24]. Overall, GO and KEGG analysis showed that these RBPs are closely related to the progress of UCEC through the above-mentioned pathways.
Subsequently, a PPI network was constructed based on these abnormally expressed RBPs. We obtained 145 key RBPs from three key modules. It has been reported that many of these key RBPs have a significant impact on tumorigenesis and tumor development. CARS is a cysteyl-tRNA synthetase, which enhances anti-tumor immunity through specific interaction with TLR2/6 of antigen presenting cells [25].
RPL22L1 is a ribosomal protein that can regulate the splicing of mRNA precursors [26]. Studies have found that RPL22L1 is highly expressed in tumor tissues and participates in the proliferation and metastasis of tumor cells[27, 28].
Univariate Cox regression analysis was performed to analyze and screen the central RBP related to prognosis. We finally identified 631 RBP coding genes. Next, through multiple stepwise Cox regression analysis, 6 RBPs were used to construct a risk model to predict the prognosis of LUSC patients. The ROC curve of the prognostic model showed that the 6-RBP gene feature (AUC = 0.799) has a moderate performance in OS. Multivariate Cox regression analysis showed that this risk-sharing model can independently predict the prognosis of UCEC patients. The immunohistochemistry expression levels of 6 RBPs were verified by HPA database. Constructed a nomogram to help clinicians predict the prognosis of UCEC patients. In summary, our prediction model is relatively reliable and could be used to identify UCEC patients with a poor prognosis, which is helpful for the early diagnosis and treatment of UCEC patients.
This study has certain limitations. First, our results are only based on RNA sequencing; in addition, our prognostic model is built on the UCEC data set of the TCGA and GEO databases, and has not been validated by the clinical patient cohort; finally, for the selected RBP The specific role of UCEC should be carried out in vitro experiments and animal experiments to reveal the mechanism.