AUTHOR=Nie Ye , Li Jianhui , Wu Wenlong , Guo Dongnan , Lei Xinjun , Zhang Tianchen , Wang Yanfang , Mao Zhenzhen , Zhang Xuan , Song Wenjie 

TITLE=A Novel Nine-lncRNA Risk Signature Correlates With Immunotherapy in Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.706915

DOI=10.3389/fonc.2021.706915

ISSN=2234-943X

ABSTRACT=Background：Hepatocellular carcinoma is one of the most common malignant tumors with a very high mortality rate. The emergence of immunotherapy has brought hope for the cure of hepatocellular carcinoma. Only a small number of patients respond to immune checkpoint inhibitors, ferroptosis and tertiary lymphoid structure contribute to the increased response rate of immune checkpoint inhibitors, so we first need to identify those who are sensitive to immunotherapy, and then develop different methods to improve sensitivity for different groups.
Methods：The sequencing data of hepatocellular carcinoma from the Cancer Genome Atlas and  Gene Expression Omnibus was downloaded to identify the immune-related LncRNAs. LncRNAs related to survival data were screened out, and a risk signature was established using Cox proportional hazard regression model. R software was used to calculate the riskScore of each patient, and the patients were divided into high risk group and low risk group. The prognostic value of riskScore and its application in clinical chemotherapeutic drugs were confirmed. The relationship between riskScore and immune checkpoint genes, ferroptosis genes and genes related to tertiary lymphoid structure formation was analyzed by Spearman method. TIMER, CIBERSORT, ssGSEA and ImmuCellAI were used to evaluate the relative number of lymphocytes in tumor. The Wilcoxon signed-rank test confirmed differences in immunophenoscore between the high risk and low risk groups. 
Results：Data analysis revealed that our signature could well predict the 1year, 2 year, 3yearand 5year survival rates of hepatocellular carcinoma, as well as to predict susceptible populations with Sorafenib. The risk signature were significantly correlated with immune checkpoint genes, ferroptosis genes, and tertiary lymphoid structure-forming genes, as well as predicting tumor-infiltrating lymphocyte status. There was a significant difference in IPS scores between the low risk group and the high risk group, while the low risk group had higher scores. 
Conclusion：The riskScore obtained from an immune-related lncRNA signature could successfully predict the survival time and reflect the efficacy of immune checkpoint inhibitors. More importantly, it is possible to select different treatments for different hepatocellular carcinoma patients that increase the response rate of immune checkpoint inhibitors, and will help improve the individualized treatment of hepatocellular carcinoma.