Discovery and validation of immune- related long non-coding RNA biomarkers associated with prognosis in hepatocellular carcinoma

Abstract

Background : Hepatocellular carcinoma (HCC) is one of the most common clinical malignant tumors, resulting in high mortality and poor prognosis. Studies have found that LncRNA plays an important role in the onset, metastasis and recurrence of hepatocellular carcinoma. The immune system plays a vital role in the development, progression, metastasis and recurrence of cancer. Therefore, immune-related lncRNA can be used as a novel biomarker to predict the prognosis of hepatocellular carcinoma. Methods : The transcriptome data and clinical data of HCC patients were obtained by using The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA‑LIHC), and immune-related genes were extracted from the Molecular Signatures Database (IMMUNE RESPONSE M19817 and IMMUNE SYSTEM PROCESS M13664). By constructing the co-expression network and Cox regression analysis, 13 immune-lncRNAs was identified to predict the prognosis of HCC patients. Patients were divided into high risk group and low risk group by using the risk score formula, and the difference in overall survival (OS) between the two groups was reflected by Kaplan-Meier survival curve. The time - dependent receiver operating characteristics (ROC) analysis and principal component analysis (PCA) were used to evaluate 13 immune -lncRNAs signature. Results : Through TCGA - LIHC extracted from 343 cases of patients with hepatocellular carcinoma RNA - Seq data and clinical data, 331 immune-related genes were extracted from the Molecular Signatures Database , co-expression networks and Cox regression analysis were constructed, 13 immune-lncRNAs signature was identified as biomarkers to predict the prognosis of patients. At the same time using the risk score median divided the patients into high risk and low risk groups, and through the Kaplan-Meier survival curve analysis found that high-risk group of patients' overall survival (OS) less low risk group of patients. The AUC value of the ROC curve is 0.828, and principal component analysis (PCA) results showed that patients could be clearly divided into two parts by immune-lncRNAs, which provided evidence for the use of 13 immune-lncRNAs signature as prognostic markers. Conclusion : Our study identified 13 immune-lncRNAs signature that can effectively predict the prognosis of HCC patients, which may be a new prognostic indicator for predicting clinical outcomes.

The Association between Long Noncoding RNA over Expression and Poor Prognosis of Liver Cancer: A Meta-Analysis

“…A total of 7 studies [ 16 , 20 , 29 , 31 , 33 , 41 , 52 ] were included. The meta-analysis of the fixed effects model (I 2 = 38.1%, P = 0.138) showed that compared with patients with low expression of lncRNA, patients with high expression of lncRNA have shorter DFS.…”

“…ese outcomes suggest that different types of lncRNA play different characters, but they all have significant roles in the growth and prognosis of liver cancer. Li 2017 [16] Ding 2015 [20] Zhang2020 [29] Xiao2020 [31] Nie2019 [33] Zhou2019 [41] Liang2021 [52] Overall, DL (I individuals. e results show that vascular invasion, histological grade, number of tumors, size of the tumor, metastasis, and TNM stage of liver cancer patients are associated with the expression level of lncRNA.…”

“…A total of 7 studies [16,20,29,31,33,41,52] Cutoff value: the critical value to distinguish between high and low lncRNA expression; OS : overall survival; mean ratio: average expression level of lncRNA; median value: median expression level of LncRNA; -: no mention in text; OS : overall survival; DFS : disease-free survival; RFS : relapse-free survival; both: reported in text and survival curve; SDD : surgery to the date of death.…”

“…Results of meta-analysis on the correlation between LncRNA expression level and clinical features of liver cancer. Tumor number 25[10,16,24,26,29,31,34,35,37,42,43,46,48,50,51,55] 53.4% 0.001 Random 0.72 (0.62,0.84) <0.001 V-invasion 22 [16, 19, 24, 26, 30, 32, 35, 37, 41, 42, 44, 45, 47, 49, 51, 55] 84.7% <0.001 Random 2.02 (1.74,2.35) <0.001 AFP (400): the cutoff of AFP is 400 μg/L; AFP (20): the cutoff of AFP is 20 μg/L; H-grade: histological grade; V-invasion: vascular invasion.…”