尼古丁是烟草的成分，其暴露会增加各种癌症风险，包括口腔癌。以往的研究主要关注其成瘾性质，但其致癌机制鲜有研究。本研究旨在通过数据挖掘和实验验证探索尼古丁促进口腔癌发生和发展的关键基因。 本研究分为三个部分。首先，通过数据挖掘筛选出与尼古丁相关的口腔癌的关键基因；其次，利用生物信息学验证了这些关键基因在口腔癌组织中的表达和临床意义。最后，通过组织学调查关键基因在口腔癌中的表达和临床意义，并细胞学评估其表达对细胞增殖、侵袭和耐药性的影响。 SERPINE1被鉴定为关键基因，尼古丁处理的口腔细胞中表达上调，可能是口腔癌的独立预后因子。SERPINE1富集在多种通路中，如TNF和Apelin通路；并与巨噬细胞、CD4+T细胞和CD8+T细胞的渗透有关。SERPINE1的过表达与N分期有关，可能涉及缺氧、血管生成和转移。抑制口腔癌细胞中SERPINE1的表达可减弱其增殖和侵袭能力，提高其对Bleomycin和Docetaxel的敏感性。 本研究揭示了SERPINE1作为尼古丁相关口腔癌的关键基因，表明SERPINE1可能是口腔癌的新型预后指标和治疗靶点。

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.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.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.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.