AUTHOR=Zhao Zihuan , Zhao Dan , Xia Ji , Wang Yi , Wang Buhai 

TITLE=Immunoscore Predicts Survival in Early-Stage Lung Adenocarcinoma Patients

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00691

DOI=10.3389/fonc.2020.00691

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> The lung cancer staging system is insufficient for a comprehensive evaluation of patient prognosis. We constructed a novel immunoscore model to predict patients with high risk and poor survival.</p><p><bold>Method:</bold> Immunoscore was developed based on z-score transformed enrichment score of 11 immune-related gene sets of 109 immune risk genes. The immunoscore model was trained in lung adenocarcinoma cohort from The Cancer Genome Atlas (TCGA-LUAD) (<italic>n</italic> = 400), and validated in other two independent cohorts from Gene Expression Omnibus (GEO), GSE31210 (<italic>n</italic> = 219) and GSE68465 (<italic>n</italic> = 356). Meta-set (<italic>n</italic> = 975) was formed by combining all training and testing sets.</p><p><bold>Result:</bold> High immunoscore conferred worse prognosis in all sets. It was an independent prognostic factors in multivariate Cox analysis in training, testing and meta-set [hazard ratio (HR) = 2.96 (2.24–3.9), <italic>P</italic> &lt; 0.001 in training set; HR = 1.99 (1.21–3.26), <italic>P</italic> = 0.006 in testing set 1; HR = 1.48 (1.69–2.39), <italic>P</italic> = 0.005 in testing set 2; HR = 2.01 (1.69–2.39), <italic>P</italic> &lt; 0.001 in meta-set]. Immunoscore-clinical prognostic signature (ICPS) was developed by integrating immunoscore and clinical characteristic, and had higher C-index than immunoscore or stage alone in all sets [0.72 (ICPS) vs. 0.7 (immunoscore) or 0.59 (stage) in training set; 0.75 vs. 0.72 or 0.7 in testing set 1; 0.65 vs. 0.61 or 0.62 in testing set 2; 0.7 vs. 0.66 or 0.64 in meta-set]. Genome analysis revealed that immunoscore was positively correlated with tumor mutation burden (<italic>R</italic> = 0.22, <italic>P</italic> &lt; 0.001). Besides, high immunoscore was correlated with high proportion of carcinoma-associated fibroblasts (<italic>R</italic> = 0.32, <italic>P</italic> &lt; 0.001) in tumor microenvironment but fewer CD8+ cells infiltration (<italic>R</italic> = −0.28, <italic>P</italic> &lt; 0.001).</p><p><bold>Conclusion:</bold> The immunoscore and ICPS are potential biomarkers for evaluating patient survival. Further investigations are required to validate and improve their prediction accuracy.</p>