Validation of an Immune-Related Gene Pair Index as a Prognostic Marker of Lung Squamous Cell Carcinoma

Abstract Background: Lung squamous cell carcinoma (LUSC) is one of the subtypes of non-small-cell lung cancer (NSCLC) and accounts for approximately 20 to 30% of all lung cancers. Methods: In this study, we developed an immune-related gene pair index (IRGPI) for LUSC from 8 public LUSC data sets, including The Cancer Genome Atlas LUSC cohort and Gene Expression Omnibus data sets, and explored the prognostic value of IRGPI for patients with LUSC. Results: IRGPI was constructed by 13 gene pairs consisting of 25 unique immune-related genes from the training cohort. Multivariate cox regression analysis showed that high risk based on IRGPI was an independent risk factor for poor prognosis of patients with LUSC in the training cohort (230 patients; HR= 3.40; 95%CI [2.34-4.94]; p<0.001), the testing cohort (228 patients; HR=2.11; 95%CI [1.48-3.01]; p<0.001) and the validation cohort (472 patients; HR=1.99; 95%CI [1.5-2.63]; p<0.001). The infiltrations of naïve B cells, plasma cells, CD8+ T cells, activated memory CD4+ T cells, gamma delta (γδ) T cells, M1 macrophages, and activated dendritic cells were lower in the high-risk group, as compared with the low-risk group in the TCGA cohort. The infiltrations of neutrophils, activated mast cells, and monocytes were higher in the high-risk group. Conclusions: IRGPI is a significant prognostic biomarker for predicting overall survival in LUSC patients. Combining clinical features with IRGPI will improve prognostic accuracy.