Abstract
Hepatocellular carcinoma (HCC) ranks fifth among common cancers and is the second most common cause of cancer-related mortality worldwide. This study is aimed at identifying an immune-related long noncoding RNA (lncRNA) signature as a potential biomarker with prognostic value to improve early diagnosis and provide potential therapeutic targets for HCC patients. The subjects of this study were HCC samples with complete transcriptome data and clinical information downloaded from The Cancer Genome Atlas (TCGA) database. We then extracted the immune-related mRNA and lncRNA expression profiles. Based on the expression profiles of immune-related lncRNAs, we identified a nine-lncRNA signature that was related to the progression of HCC. The risk score was calculated based on the expression level of the nine lncRNAs of each sample, which divided patients into high-risk and low-risk groups. We found that the increased risk score was associated with a poor prognosis of HCC patients. To assess the accuracy of the survival model, we calculated a receiver operating characteristic (ROC) for validation. The curve showed that the area under the curve (AUC) for the risk score was 0.792. Besides, both principal component analysis (PCA) and gene set enrichment analysis (GSEA) were further used for functional annotation. We found that the distribution patterns were different between the low-risk and high-risk groups in PCA, and the underlying mechanism by which the nine lncRNAs promoted the progression of HCC involved an abnormal immune status. Finally, we analyzed the infiltration of twenty-nine kinds of immune cells and the activation of immune function in HCC using the ssGSEA algorithm. The results showed that aDCs, iDCs, macrophages, Tfh, Th1, Treg, and NK cells were correlated with the progress of HCC patients. And the immune functions including APC costimulation, CCR, check point, HLA, MHC class I, and Type II IFN responses were also significantly different between the high-risk and low-risk groups. In conclusion, our study identified a nine-lncRNA signature with potential prognostic value for patients with HCC, which could be used as a new biomarker for the diagnosis and immunotherapy of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for approximately 90% of cases, and it has become a public health problem worldwide [1, 2]
A total of 331 immune-related mRNAs were collected based on the Molecular Signatures Database v7.0, and 338 immune-related long noncoding RNA (lncRNA) were identified from the correlation analysis (∣cor ∣ >0:4, p < 0:001)
The results show that the area under the curve (AUC) value of the risk score model receiver operating characteristic (ROC) curve was 0.792, indicating that the nine-lncRNA signature was effective in predicting the overall survival (OS) of the HCC patients (Figure 3(b))
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for approximately 90% of cases, and it has become a public health problem worldwide [1, 2]. Over the past few decades, the prevalence of chronic hepatitis, liver cirrhosis, the difficulty of early diagnosis of HCC, and the limited efficacy of available treatments are the major reasons contributing to the continuous increase of the incidence of HCC [3, 4]. It has become the second most common malignant tumor in the world, with an overall 5-year survival rate of less than 50% [5, 6]. It is necessary to consider the immune-related factors related to the prognosis of patients with HCC
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