Identification of diagnostic long non‑coding RNA biomarkers in patients with hepatocellular carcinoma

Abstract

Liver cancer is a leading cause of cancer-associated mortality worldwide. Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. The aim of the present study was to identify long non-coding RNA (lncRNAs) as diagnostic biomarkers for HCC. The lncRNA and mRNA expression profiles of a large group of patients with HCC were obtained from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) and the differentially expressed mRNAs (DEmRNAs) were identified by bioinformatics analysis. Using feature selection procedure and a classification model, the optimal diagnostic lncRNA biomarkers for HCC were identified. Classification models, including random forests, decision tree and support vector machine (SVM), were established to distinguish between HCC and normal tissues. DEmRNAs co-expressed with the lncRNAs were considered as targets of DElncRNAs. Functional annotation of DEmRNAs co-expressed with these lncRNAs biomarkers was performed. Receiver operating characteristic curve analysis of lncRNAs biomarkers was conducted. A total of 3,177 lncRNAs and 15,183 mRNAs between HCC and normal tissues were obtained. RP11-486O12.2, RP11-863K10.7, LINC01093 and RP11-273G15.2 were identified as optimal diagnostic lncRNA biomarkers for HCC that were co-expressed with 273, 69, 76 and 1 DEmRNAs, respectively. The area under the curve values of the random forest model, decision tree model and SVM model were 0.992, 0.927 and 0.992, and the specificity and sensitivity of the three models were 100.0 and 95.6, 92.0 and 98.3 and 98.0 and 97.2%, respectively. ‘PPAR signaling pathway’ and ‘retinol metabolism’ were two significantly enriched target pathways of DElncRNAs. The present study identified four DElncRNAs, including RP11-486O12.2, RP11-863K10.7, LINC01093 and RP11-273G15.2, as potential diagnostic biomarkers of HCC. Functional annotation of target DEmRNAs provided novel evidence for examining the precise roles of lncRNA in HCC.

Low expression of long noncoding RNA CTC‐297N7.9 predicts poor prognosis in patients with hepatocellular carcinoma

“…Recent research pointed out that lncRNA CTC‐297N7.9 was differentially expressed in HCC and normal liver tissues. According to the TCGA database, its expression is significantly associated with the survival of HCC patients . CTC‐297N7.9 was also reported to participate in the construction of prognostic models that identified the role of lncRNA as a protective factor in HCC .…”

Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy

“…Through analysis of data generated from the cancer genome atlas (TCGA) consortium, Li et al constructed mRNA-lncRNA coexpression networks. The expression pattern of coding and non-coding transcripts in HCC led to the identification of several lncRNAs that could potentially be used as biomarkers for HCC [185]. Although these lncRNAs were not able to predict the outcome of patients, these lncRNAs show promise for the diagnostic setting.…”

PITPNA-AS1 abrogates the inhibition of miR-876-5p on WNT5A to facilitate hepatocellular carcinoma progression

“…For examples, lncRNA EGFR-AS1 accelerates cell growth and metastasis of renal carcinoma by affecting HuR-stabilized EGFR 9 ; lncRNA MEG3 represses cellular proliferation and stimulates apoptosis in prostate cancer 10 ; PCGEM1 boosts the tumorigenesis and exacerbation of ovarian cancer by RhoA pathway 11 ; and lncRNA GAS5 suppresses cell cycle through binding to YBX1 so as to modulate p21 in stomach cancer 12 . Importantly, reports about the association between lncRNAs and liver cancer have been increasing in recent years 13,14 . Biological role of dysregulated lncRNAs has been unveiled in HCC progress 15,16 .…”