SERPINE1 as an independent prognostic marker and therapeutic target for nicotine-related oral carcinoma

Background: Nicotine is an ingredient of tobacco, and its exposure increases various cancer risks, including oral cancer. Previous studies have focused on its addictive properties, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process of nicotine promoting the occurrence and development of oral cancer through data mining and experimental verification. Methods: This study involved three parts. First, the key genes related to nicotine-related oral cancer were screened out through data mining; second, the expression and clinical significance of the key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.Results: SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways such as TNF and Apelin pathways; and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to Bleomycin and Docetaxel. Conclusion: This study revealed SERPINE1 as the key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.