AUTHOR=Sun Rui , Wang Xu , Chen Jiajie , Teng Da , Chan Shixin , Tu Xucan , Wang Zhenglin , Zuo Xiaomin , Wei Xiang , Lin Li , Zhang Qing , Zhang Xiaomin , Tang Kechao , Zhang Huabing , Chen Wei 

TITLE=Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.949110

DOI=10.3389/fgene.2022.949110

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs.</p><p><bold>Method:</bold> Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan–Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of <italic>AC026412.3</italic>, <italic>AL451069.3</italic>, and <italic>AL031985.3</italic> in normal hepatic and HCC cell lines.</p><p><bold>Results:</bold> We identified 3 srlncRNAs (<italic>AC026412.3</italic>, <italic>AL451069.3</italic>, and <italic>AL031985.3</italic>) and constructed a new risk model. The results of the ROC curve and Kaplan–Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines.</p><p><bold>Conclusion:</bold> The novel srlncRNA (<italic>AC026412.3</italic>, <italic>AL451069.3</italic>, and <italic>AL031985.3</italic>) signatures may provide insights into new therapies and prognosis predictions for patients with HCC.</p>