Abstract
The relationship between m6A-related lncRNAs and prognosis in hepatocellular carcinoma (HCC) is not yet clear. We used Lasso regression to establish a prognostic signature based on m6A-related lncRNAs using a training set from TCGA, and then verified the signature efficacy in a test set. Fluorescence quantitative real-time PCR (qPCR), Survival analysis, clinical risk difference analysis, immune-related analysis, and drug-sensitivity analysis were conducted. The results revealed that 1,651 lncRNAs were differentially expressed in HCC tissues, among which, 163 were m6A-related. Univariate analysis showed that 87 lncRNAs were associated with the overall survival. Six differential m6A-related lncRNAs were validated and selected via Lasso regression to construct a prognostic signature which demonstrated a satisfactory predictive efficacy. In the clinically relevant pathologic stage, histologic grade, and T stage, the risk scores obtained based on this signature showed a statistically significant difference. The high- and low-risk groups exhibited a difference in the tumor immune infiltrating cells, immune checkpoint gene expression, and sensitivity to chemotherapy. In summary, the prognostic signature based on the m6A-related lncRNAs can effectively predict the prognosis of patients and might provide a new vista for the chemotherapy and immunotherapy of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the seventh most common form of cancer and the second most frequent cause of cancer-related mortality in the world
The purpose of this study is to explore the differences in m6Arelated Long noncoding RNA (lncRNA) of HCC and establish an effective prognostic signature
Given that m6A-related genes play an important role in the occurrence and development of HCC, we believe that the m6A-related lncRNAs are more likely to affect the prognosis of HCC and can form a more meaningful signature, so in our signature, only the m6A-related lncRNAs are retained for subsequent analysis
Summary
Hepatocellular carcinoma (HCC) is the seventh most common form of cancer and the second most frequent cause of cancer-related mortality in the world. Its incidence is on the rise, posing a serious threat to human health [1]. There are multiple ways to treat HCC, such as partial hepatectomy, liver transplantation, radiofrequency ablation, hepatic artery embolization chemotherapy, and targeted therapy and immunotherapy. The efficacy of these therapies is limited by the high recurrence rates and high metastasis rates of HCC [2]. The 5-year survival rate of HCC is only 18.4% in some developed countries clinical technologies have advanced in recent years [3], and much lower in less developed countries because of access barriers to diagnosis and treatment. Due to the complex molecular mechanism of HCC
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