AUTHOR=Li Qiaxuan , Yao Lintong , Lin Zenan , Li Fasheng , Xie Daipeng , Li Congsen , Zhan Weijie , Lin Weihuan , Huang Luyu , Wu Shaowei , Zhou Haiyu TITLE=Identification of Prognostic Model Based on Immune-Related LncRNAs in Stage I-III Non-Small Cell Lung Cancer JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.706616 DOI=10.3389/fonc.2021.706616 ISSN=2234-943X ABSTRACT=Background

Long non-coding RNAs (lncRNAs) participate in the regulation of immune response and carcinogenesis, shaping tumor immune microenvironment, which could be utilized in the construction of prognostic signatures for non-small cell lung cancer (NSCLC) as supplements.

Methods

Data of patients with stage I-III NSCLC was downloaded from online databases. The least absolute shrinkage and selection operator was used to construct a lncRNA-based prognostic model. Differences in tumor immune microenvironments and pathways were explored for high-risk and low-risk groups, stratified by the model. We explored the potential association between the model and immunotherapy by the tumor immune dysfunction and exclusion algorithm.

Results

Our study extracted 15 immune-related lncRNAs to construct a prognostic model. Survival analysis suggested better survival probability in low-risk group in training and validation cohorts. The combination of tumor, node, and metastasis staging systems with immune-related lncRNA signatures presented higher prognostic efficacy than tumor, node, and metastasis staging systems. Single sample gene set enrichment analysis showed higher infiltration abundance in the low-risk group, including B cells (p<0.001), activated CD8+ T cells (p<0.01), CD4+ T cells (p<0.001), activated dendritic cells (p<0.01), and CD56+ Natural killer cells (p<0.01). Low-risk patients had significantly higher immune scores and estimated scores from the ESTIMATE algorithm. The predicted proportion of responders to immunotherapy was higher in the low-risk group. Critical pathways in the model were enriched in immune response and cytoskeleton.

Conclusions

Our immune-related lncRNA model could describe the immune contexture of tumor microenvironments and facilitate clinical therapeutic strategies by improving the prognostic efficacy of traditional tumor staging systems.