Identification of heterogeneous nuclear ribonucleoprotein as a candidate biomarker for diagnosis and prognosis of hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate. However, spliceosomal genes are still lacking in the diagnosis and prognosis of HCC.Methods: Identification of differentially expressed genes (DEGs) was performed using the limma package in R software. Modules highly related to HCC were obtained by weighted gene co-expression network analysis (WGCNA), and the module genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The biomarker for diagnosing HCC was determined by receiver operating characteristic (ROC) curve analysis, and the effect of the biomarker in the diagnosis of HCC was evaluated by performing five-fold cross-validation with logistic regression. HCC specimens from preoperatively treated patients were tested for biomarker by real-time quantitative polymerase chain reaction (RT-qPCR).Kaplan-Meier analysis was used to assess the relationship between biomarker and patient survival. The role of biomarker was evaluated using ESTIMATE analysis in the tumor microenvironment.Results: In this study, 389 DEGs were screened out from three Gene Expression Omnibus (GEO) datasets.We also found that the turquoise module of 123 genes from The Cancer Genome Atlas (TCGA) data was the key module with the highest correlation with HCC traits. Then, 123 genes were analyzed using the KEGG enrichment pathway, and eight genes were found to be most significantly related to the spliceosome pathway. We selected 8 genes and 389 DEGs shared genes, and finally got the only gene, heterogeneous nuclear ribonucleoprotein (hnRNPU). The high expression of hnRNPU was associated with poor prognosis of HCC, and hnRNPU was a biomarker for diagnosing HCC. In the tissues of patients with excellent HCC treatment hnRNPU messenger RNA (mRNA) was lower than in the tissues of patients with poor HCC treatment. High expression of hnRNPU was significantly increased in HCC patients with low stromal (P<0.05), low immune (P<0.05), and low estimation scores (P<0.05), and with high tumor purity (P<0.05) and high malignant progression (P<0.05) of the HCC. Conclusions:The hnRNPU gene identified in this study may become a new biomarker for the diagnosis and prognosis of HCC.

Functional analysis of hepatic long non‐coding ribonucleic acids during liver transplantation in humans

“…It has been proposed that HNRNPU can be used as a screening marker for HCC and even as one of the intervention targets of transcription factors such as Myc. 61,62 Because the growing shortage of liver grafts across the world has resulted in the use of livers with a low degree of steatosis as a marginal graft under emergency circumstances, exacerbated HIRI, abnormal lipids metabolism, and delayed recovery with marginal graft after liver transplantation 63 remain as major issues that need to be addressed.…”

“…Currently, studies on HNRNPU in normal liver tissues are limited, but HNRNPU over‐expression in HCC tissues was highly related to poor prognosis of HCC. It has been proposed that HNRNPU can be used as a screening marker for HCC and even as one of the intervention targets of transcription factors such as Myc 61,62 …”