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.