Validation of an Immune-related Gene Pair Index as a Prognostic Marker of Early-Stage 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 early-stage LUSC from 3 public LUSC data sets, including The Cancer Genome Atlas LUSC cohort and Gene Expression Omnibus data sets, and explored whether IRGPI could act as a prognostic marker to identify patients with early-stage LUSC at high risk.Results. IRGPI was constructed by 68 gene pairs consisting of 123 unique immune-related genes from TCGA LUSC cohort. In the derivation cohort, the hazard of death among high-risk group was 10.51 times that of the low-risk group (HR, 10.51; 95%CI, 6.96-15.86; p<0.001). The hazard of death among the high-risk group was 2.26 times that of the low-risk group (HR, 2.26; 95%CI, 1.2-4.25; p=0.009) in the GSE37745 validation cohort and was 3.2 times that of low-risk group (HR, 3.2; 95%CI, 0.98-10.4; p=0.042) in the GSE41271 validation cohort. The infiltrations of CD8+ T cells and T follicular helper cells were lower in the high-risk group, as compared with the low-risk group in the TCGA cohort (6.94% vs 9.63%, p=0.004; 2.15% vs 3%, p=0.002, respectively). The infiltrations of neutrophils, activated mast cells and monocytes were higher in the high-risk group, as compared with the low-risk group in the TCGA cohort (1.63% vs 0.72%, p=0.001; 1.64% vs 1.02%, p=0.007; 0.57% vs 0.35%, p=0.041, respectively).Conclusions. IRGPI is a significant prognostic biomarker for predicting overall survival in early-stage LUSC patients.