Abstract
Liver cancer is the most common cancer and is the epitome of a recalcitrant cancer. Increasing evidence shown that long noncoding RNAs (lncRNA) were associated with cancer‐related death and could function as a competing endogenous RNA (ceRNA). To explore regulatory roles and potential prognostic biomarkers of lncRNA for liver cancer, RNA‐sequencing expression data were downloaded from the TCGA database and GEO database. A total of 357 patients were randomly divided into a discovery group and a validation group, of which 313 patients can obtain clinical data. In discovery phrase, 58 lncRNAs, 16 miRNAs, and 34 mRNAs were screened to construct the ceRNA network based on 252 patients employed from discovery group. Univariate and multivariate Cox hazard regression analysis model revealed that five lncRNAs (AATK‐AS1, C10orf91, LINC00162, LINC00200, and LINC00501) from 58 lncRNAs were formulated to predict the overall survival (OS). We used the value of gene expression and regression coefficients to construct a risk score based on the five lncRNAs. Next, we validated our model in the GSE116174 dataset (n = 64) and the validation group (n = 94) from TCGA database. Subgroup analysis suggest that the five lncRNAs played critical parts in early stage in cancer from both discovery and validation groups. The five lncRNAs were also found to be associated with immune cells infiltration including CD4+ memory activated, NK cells activated and mast cells activated, then the results were also validated according to the validation group. Furthermore, KEGG pathway enrichment analysis showed that these nine coexpressed modules using the method of WGCNA, and many of these pathways are associated with the development and progression of disease. At last, the transcription factor binding sites (TFBS) of the five lncRNAs were predicted, which help us to understand the potential mechanism that the TFBS adjusted the ceRNA network. In summary, the ceRNA regulatory network may contribute to a better understanding of liver cancer mechanism and provide potential prognostic biomarkers and therapeutic targets.
Highlights
Hepatocellular carcinoma (HCC) became the sixth common cancer and the death rate increased year by year.[1]
The assessment model was validated in validation and entire group, and we further explore biological function as well as immune cells infiltration characters associated with the five long noncoding RNAs (lncRNA), we predicted the transcription factor binding sites (TFBS) of HCC which may regulate the competing endogenous RNA (ceRNA) network to understand the potential mechanism
The novel hypothesis has been confirmed that each RNA sharing the same miRNA response elements (MRE) could interact with or compete each other, which present a new mechanism of gene expression regulation that could be used to further understand of various diseases including cancer
Summary
Hepatocellular carcinoma (HCC) became the sixth common cancer and the death rate increased year by year.[1]. With the development of experimental studies and techniques for lncRNA discovery, lncRNA‐associated ceRNA networks have been constructed and analyzed in colorectal cancer, gastric cancer, and osteosarcoma.[13,16,17] there existed fewer analysis of ceRNA network in hepatocellular carcinoma (HCC). We conducted a comprehensive analysis of mRNA, lncRNA, and miRNA expression profiles in HCC and the lncRNA‐sequencing (lncRNA‐seq) data, mRNA‐seq, and miRNA‐seq expression of HCC samples were downloaded from TCGA database and the differently expressed RNAs were screened to construct ceRNA network. The assessment model was validated in validation and entire group, and we further explore biological function as well as immune cells infiltration characters associated with the five lncRNAs, we predicted the TFBS of HCC which may regulate the ceRNA network to understand the potential mechanism
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