Characterization of a prognostic model for lung squamous cell carcinoma based on eight stemness index-related genes.

Abstract

BackgroundCancer stem cells (CSCs) are implicated in cancer progression, chemoresistance, and poor prognosis; thus, they may be promising therapeutic targets. In this study, we aimed to investigate the prognostic application of differentially expressed CSC-related genes in lung squamous cell carcinoma (LUSC).MethodsThe mRNA stemness index (mRNAsi)-related differentially expressed genes (DEGs) in tumors were identified and further categorized by LASSO Cox regression analysis and 1,000-fold cross-validation, followed by the construction of a prognostic score model for risk stratification. The fractions of tumor-infiltrating immune cells and immune checkpoint genes were analyzed in different risk groups.ResultsWe found 404 mRNAsi-related DEGs in LUSC, 77 of which were significantly associated with overall survival. An eight-gene prognostic signature (PPP1R27, TLX2, ANKLE1, TIGD3, AMH, KCNK3, FLRT3, and PPBP) was identified and used to construct a risk score model. The TCGA set was dichotomized into two risk groups that differed significantly (p = 0.00057) in terms of overall survival time (1, 3, 5-year AUC = 0.830, 0.749, and 0.749, respectively). The model performed well in two independent GEO datasets (p = 0.029, 0.033; 1-year AUC = 0747, 0.783; 3-year AUC = 0.746, 0.737; 5-year AUC = 0.706, 0.723). Low-risk patients had markedly increased numbers of CD8+ T cells and M1 macrophages and downregulated immune checkpoint genes compared to the corresponding values in high-risk patients (p < 0.05).ConclusionA stemness-related prognostic model based on eight prognostic genes in LUSC was developed and validated. The results of this study would have prognostic and therapeutic implications.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12890-022-02011-0.