Identification of JAK2 and FOXM1 expression as novel candidate biomarkers for predicting the benefit of immunotherapy in lung squamous cell carcinoma.

Background Lung squamous cell carcinoma (LUSC) accounts for about 30% of all non-small cell lung cancers (NSCLC). However, only a small percentage of LUSC patients gain benefit from immune checkpoint inhibitors (ICIs). Methods This study analyzed LUSC patients from The Cancer Genome Atlas (TCGA), which were divided into 2 groups: PD-L1 high-expression/TMB-high (TPH) and PD-L1 low-expression/TMB-low (TPL) group based on programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) status. The differences in tumor-infiltrating immune cells were estimated between the 2 groups. The overlap of differentially expressed genes and proteins (DEGs and DEPs) between 2 groups were used as candidate biomarkers. Kaplan-Meier curves were used to evaluate the association between risk score and overall survival (OS). Results More abundant immune infiltration fractions were found in TPH group. Janus kinase 2 (JAK2) and forkhead box protein M1 (FOXM1) were identified as DEGs between the TPH and TPL groups. Subsequently, we developed a risk score that combined the expression of JAK2 and FOXM1 in an effort to accurately determine the survival risk of LUSC patients. Patients with high-risk [hazard ratio (HR), median OS, 43.1 months 1.924; 95% confidence interval (CI): 1.256 to 2.945; P=0.002) had shorter survival than those with low-risk (median OS, 70.0 months). External data verification found that JAK2 and FOXM1 were significantly expressed at a higher level in the responders receiving immunotherapy (P=0.038 and P=0.009, respectively). Conclusions The expressions of JAK2 and FOXM1 can be used as novel candidate biomarkers for predicting the benefit of immunotherapy in LUSC.