The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma

Abstract

The aim of the present study is to construct a competitive endogenous RNA (ceRNA) regulatory network by using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with hepatocellular carcinoma (HCC), and to construct a prognostic model for predicting overall survival (OS) of HCC patients. Differentially expressed lncRNAs, miRNAs, and mRNAs were explored between HCC tissues and normal liver tissues. A prognostic model was built for predicting OS of HCC patients and receiver operating characteristic curves were used to evaluate the performance of the prognostic model. There were 455 differentially expressed lncRNAs, 181 differentially expressed miRNAs, and 5035 differentially expressed mRNAs. A ceRNA regulatory network was constructed based on 43 lncRNAs, 37 miRNAs, and 105 mRNAs. Eight mRNA biomarkers (H2AFX, SQSTM1, ITM2A, PFKP, TPD52L1, ACSL4, STRN3, and CPEB3) were identified as independent risk factors by multivariate Cox regression and were used to develop a prognostic model for OS. The C‐indexes in the model group were 0.776 (95% confidence interval [CI], 0.730‐0.822), 0.745 (95% CI, 0.699‐0.791), and 0.789 (95% CI, 0.743‐0.835) for 1‐, 3‐, and 5‐year OS, respectively. The current study revealed potential molecular biological regulation pathways and prognostic biomarkers by the ceRNA regulatory network. A prognostic model based on prognostic mRNAs in the ceRNA network might be helpful to predict the individual mortality risk for HCC patients. The individual mortality risk calculator can be used by visiting the following URL: https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/.

Identification of an Autophagy-Related Gene Signature that Can Improve Prognosis of Hepatocellular Carcinoma Patients

“…Indeed, phosphorylated SQSTM1/p62 has been shown to accumulate in the HCC tumor region, while its inhibitor may inhibit cell proliferation and resistance to anticancer agents [37]. Furthermore, multiple studies reported that SQSTM1 could serve as a novel prognostic biomarker in multiple cancers types, including nasopharyngeal carcinoma, lung cancer, oral squamous cell carcinoma, and HCC [38][39][40][41].…”

Peer Review #1 of "Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma (v0.2)"

“…(Evert et al 2013) In addition, H2AFX together with another seven genes, constitutes a prognostic signature for HCC with C-indexes of 0.776, 0.745, and 0.789 for 1-, 3-, and 5-year OS, respectively. (Zhang et al 2019b) EZH2 is important in determining the character of hepatic tumors and immunohistochemistry results showed that this protein was positively stained in various types of malignant liver tumors. However, EZH2 has not been detected in benign hepatic diseases, such as adenomas or cirrhotic nodules.…”

An integrated analysis of the circRNA–miRNA–mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration

“…However, when we considered that all involved miRNAs and circRNAs should be significantly changed, there were only 26 miRNA-mRNA pairs and 71 circRNA-miRNA pairs remaining. Subsequently, a combination of 26 miRNA-mRNA pairs and 71 circRNA-miRNA pairs was used to construct a circRNA-miRNA-mRNA regulatory network, and was visualized using Cytoscape 3.4.0 (Figure 4), which contained 103 circRNA-miRNA-mRNA interactive groups (Table S2) and rat LR-associated circRNAs (48), miRNAs (20), and mRNAs (23).…”

“…Recently, Bai et al [20] analyzed the regulatory role of the lncRNA-miRNA-mRNA network during the proliferative phase of rat liver regeneration. Moreover, accumulating evidence has revealed that the circRNA-miRNA-mRNA regulatory network has been demonstrated to be involved in gastric cancer [21], pancreatic ductal adenocarcinoma [22], hepatocellular carcinoma [23], etc/and more.…”