AUTHOR=Wang Tao , Zhou Zhijia , Wang Xuan , You Liping , Li Wenxuan , Zheng Chao , Zhang Jinghao , Wang Lingtai , Kong Xiaoni , Gao Yueqiu , Sun Xuehua 

TITLE=Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.929035

DOI=10.3389/fgene.2022.929035

ISSN=1664-8021

ABSTRACT=Background 
Hepatocellular carcinoma (HCC) remains the most prevalent gastrointestinal 
malignancy worldwide, with robust drug resistance to therapy. N7-methylguanosine 
(m7G) mRNA modification has been significantly related to massive human diseases. 
Considering the unknown m7G-modified LncRNAs in the HCC progression, the 
study aims at investigating a prognostic signature to improve clinical outcomes and 
benefit from this for patients with HCC. 
Methods 
Two independent databases(TCGA and ICGC) allow us to analyze RNAseq data of 
HCC patients. First, co-expression analysis was applied to obtain the m7G regulator related
lncRNAs.Moreover, consensus clustering analysis was employed to divide 
HCC patients into Clusters. Then, using Lasso-Cox analysis, the m7G-related lncRNA 
prognostic signature (m7G-LPS) was first tested in the training set and then confirmed 
both in the testing and ICGC set. The m7G-LPS could divide HCC patients into two 
different risk groups(high-risk and low-risk) with the optimal risk score. Then, 
Kaplan-Meier curves, tumor mutation burden (TMB), therapeutic effects of 
chemotherapeutic agents, and expressions of immune checkpoints were performed to 
further enhance the availability of immunotherapeutic treatments for HCC patients. 
Results 
A complete of 1465 lncRNAs associated with the m7G genes were finally selected 
from the TCGA dataset, and through the univariate Cox regression, the expression 
levels of 22 m7G-lncRNAs were concerning HCC patients’ overall survival cycle 
length. Then, the whole patients were grouped into three subgroups, and 
the Cluster1s’ survival rate was longer than that for patients in Cluster2 and Cluster3. 
Further, nine prognostic m7G-relevant lncRNAs were identified to conduct the m7GLPS,
which were further verified by survival analysis, PCA, and receiver operating 
characteristic(ROC)curve. A prognostic nomogram combined age, grade, gender, 
stage and m7G-LPS showed strong reliability and accuracy in predicting survival in 
HCC patients. Finally, immune checkpoints expression, TMB, and several 
chemotherapeutic agents were remarkably associated with risk scores. More 
importantly, the OS of the high TMB patients was the worst among another three 
groups. 
Conclusion 
The prognostic model we established is validated by abundant algorithms, which 
provided a new perspective on HCC tumorigenesis and thus improved individualized 
treatments for patients.