Abstract
The progression and metastasis of oral squamous cell carcinoma (OSCC) are highly influenced by cancer stem cells (CSCs) due to their unique self-renewal and plasticity. In this study, data were obtained from a single-cell RNA-sequencing dataset (GSE172577) in the GEO database, and LASSO-Cox regression analysis was performed on 1344 CSCs-related genes to establish a six-gene prognostic signature (6-GPS) consisting of ADM, POLR1D, PTGR1, RPL35A, PGK1, and P4HA1. High-risk scores were significantly associated with unfavorable survival outcomes, and these features were thoroughly validated in the ICGC. The results of nomograms, calibration plots, and ROC curves confirmed the good prognostic accuracy of 6-GPS for OSCC. Additionally, the knockdown of ADM or POLR1D genes may significantly inhibit the proliferation, migration, and invasion of OSCC cells through the JAK/HIF-1 pathway. Furthermore, cell-cycle arrest occurred in the G1 phase by suppressing Cyclin D1. In summary, 6-GPS may play a crucial role in the occurrence and development of OSCC and has the potential to be developed further as a diagnostic, therapeutic, and prognostic tool for OSCC.