Exploring Precise Medication Strategies for OSCC Based on Single-Cell Transcriptome Analysis from a Dynamic Perspective

SIMPLE SUMMARY: At the time of diagnosis, most oral squamous cell carcinoma (OSCC) patients are in the middle or advanced stages, and advanced patients usually have poor prognosis after traditional therapy. One of the primary causes has been demonstrated to be heterogeneity. However, most of the current studies on tumor heterogeneity are static, while the development of cancer is dynamic. Thus, understanding the tumor development process from a dynamic perspective is deeply necessary. Here, we combined static and dynamic analysis based on single-cell RNA-Seq data to comprehensively dissect the complex heterogeneity and evolutionary process of OSCC. We pioneered the concept of pseudo-time score, which is closely related to patient’s prognosis. Finally, we identified candidate drugs and proposed precision medication strategies to control OSCC in two respects: treatment and blocking. Our findings offer new insights for clinical practice and could help improve the treatment of advanced OSCC. ABSTRACT: At present, most patients with oral squamous cell carcinoma (OSCC) are in the middle or advanced stages at the time of diagnosis. Advanced OSCC patients have a poor prognosis after traditional therapy, and the complex heterogeneity of OSCC has been proven to be one of the main reasons. Single-cell sequencing technology provides a powerful tool for dissecting the heterogeneity of cancer. However, most of the current studies at the single-cell level are static, while the development of cancer is a dynamic process. Thus, understanding the development of cancer from a dynamic perspective and formulating corresponding therapeutic measures for achieving precise treatment are highly necessary, and this is also one of the main study directions in the field of oncology. In this study, we combined the static and dynamic analysis methods based on single-cell RNA-Seq data to comprehensively dissect the complex heterogeneity and evolutionary process of OSCC. Subsequently, for clinical practice, we revealed the association between cancer heterogeneity and the prognosis of patients. More importantly, we pioneered the concept of pseudo-time score of patients, and we quantified the levels of heterogeneity based on the dynamic development process to evaluate the relationship between the score and the survival status at the same stage, finding that it is closely related to the prognostic status. The pseudo-time score of patients could not only reflect the tumor status of patients but also be used as an indicator of the effects of drugs on the patients so that the medication strategy can be adjusted on time. Finally, we identified candidate drugs and proposed precision medication strategies to control the condition of OSCC in two respects: treatment and blocking.