AUTHOR=Zhu Lin , Zhang Xiu-Ping , Xu Shuai , Hu Ming-Gen , Zhao Zhi-Ming , Zhao Guo-Dong , Xiao Zhao-Hui , Liu Rong TITLE=Identification of a CD4+ conventional T cells-related lncRNAs signature associated with hepatocellular carcinoma prognosis, therapy, and tumor microenvironment JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1111246 DOI=10.3389/fimmu.2022.1111246 ISSN=1664-3224 ABSTRACT=Background

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and CD4+ T lymphocytes can inhibit hepatocarcinogenesis and mediate tumor regression. However, few studies have focused on the prognostic power of CD4+ Tconv-related lncRNAs in HCC patients.

Method

We obtained data from TCGA and GEO databases and identified CD4+Tconv-related lncRNAs in HCC. The risk score was constructed using lasso regression and the model was validated using two validation cohorts. The RS was also assessed in different clinical subgroups, and a nomogram was established to further predict the patients’ outcomes. Furthermore, we estimated the immune cell infiltration and cancer-associated fibroblasts (CAFs) through TIMER databases and assessed the role of RS in immune checkpoint inhibitors response.

Results

We constructed a CD4+ Tconv-related lncRNAs risk score, including six lncRNAs (AC012073.1, AL031985.3, LINC01060, MKLN1-AS, MSC-AS1, and TMCC1-AS1), and the RS had good predictive ability in validation cohorts and most clinical subgroups. The RS and the T stage were included in the nomogram with optimum prediction and the model had comparable OS prediction power compared to the AJCC. Patients in the high-risk group had a poor immune response phenotype, with high infiltrations of macrophages, CAFs, and low infiltrations of NK cells. Immunotherapy and chemotherapy response analysis indicated that low-risk group patients had good reactions to immune checkpoint inhibitors.

Conclusion

We constructed and validated a novel CD4+ Tconv-related lncRNAs RS, with the potential predictive value of HCC patients’ survival and immunotherapy response.