Lymphovascular invasion (LOI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), is predictive of poor survival; however, the associated clinical characteristics and underlying molecular mechanisms remain largely unknown. We performed weighted gene co-expression network analysis to construct gene co-expression networks and investigate the relationship between key modules and the LOI clinical phenotype. Functional enrichment and KEGG pathway analyses were performed with differentially expressed genes. A protein–protein interaction network was constructed using Cytoscape, and module analysis was performed using MCODE. Prognostic value, expression analysis, and survival analysis were conducted using hub genes; GEPIA and the Human Protein Atlas database were used to determine the mRNA and protein expression levels of hub genes, respectively. Multivariable Cox regression analysis was used to establish a prognostic risk formula and the areas under the receiver operating characteristic curve (AUCs) were used to evaluate prediction efficiency. Finally, potential small molecular agents that could target LOI were identified with DrugBank. Ten co-expression modules in two key modules (turquoise and pink) associated with LOI were identified. Functional enrichment and KEGG pathway analysis revealed that turquoise and pink modules played significant roles in HNSCC progression. Seven hub genes (CNFN, KIF18B, KIF23, PRC1, CCNA2, DEPDC1, and TTK) in the two modules were identified and validated by survival and expression analyses, and the following prognostic risk formula was established: [risk score = EXPDEPDC1 * 0.32636 + EXPCNFN * (− 0.07544)]. The low-risk group showed better overall survival than the high-risk group (P < 0.0001), and the AUCs for 1-, 3-, and 5-year overall survival were 0.582, 0.634, and 0.636, respectively. Eight small molecular agents, namely XL844, AT7519, AT9283, alvocidib, nelarabine, benzamidine, L-glutamine, and zinc, were identified as novel candidates for controlling LOI in HNSCC (P < 0.05). The two-mRNA signature (CNFN and DEPDC1) could serve as an independent biomarker to predict LOI risk and provide new insights into the mechanisms underlying LOI in HNSCC. In addition, the small molecular agents appear promising for LOI treatment.

中文翻译：

---

与头颈部鳞状细胞癌淋巴管浸润相关的关键基因组学特征

淋巴管浸润（LOI）是头颈部鳞状细胞癌（HNSCC）的关键病理特征，预示着生存率低。然而，相关的临床特征和潜在的分子机制仍然未知。我们进行了加权基因共表达网络分析，以构建基因共表达网络，并研究关键模块与LOI临床表型之间的关系。使用差异表达的基因进行功能富集和KEGG通路分析。使用Cytoscape构建了蛋白质-蛋白质相互作用网络，并使用MCODE进行了模块分析。使用中枢基因进行预后价值，表达分析和生存分析。GEPIA和人类蛋白质图谱数据库分别用于确定毂基因的mRNA和蛋白质表达水平。使用多变量Cox回归分析建立预后风险公式，并使用受试者工作特征曲线（AUC）下的面积评估预测效率。最后，通过DrugBank确定了可能靶向LOI的潜在小分子药物。在与LOI相关的两个关键模块（绿松石和粉红色）中，确定了十个共表达模块。功能丰富和KEGG通路分析表明，绿松石和粉红色模块在HNSCC进程中起重要作用。通过生存和表达分析鉴定并验证了两个模块中的七个枢纽基因（CNFN，KIF18B，KIF23，PRC1，CCNA2，DEPDC1和TTK），并建立以下预后风险公式：[风险评分= EXPDEPDC1 * 0.32636 + EXPCNFN *（-0.07544）]。低风险组的总生存期比高风险组好（P <0.0001），并且1年，3年和5年总生存期的AUC分别为0.582、0.634和0.636。八个小分子试剂，即XL844，AT7519，AT9283，alvocidib，nelarabine，苯甲idine，L-谷氨酰胺和锌被确定为控制HNSCC LOI的新候选药物（P <0.05）。两个mRNA签名（CNFN和DEPDC1）可以用作预测LOI风险的独立生物标志物，并为HNSCC中LOI的潜在机制提供新见解。此外，小分子药物似乎有望用于LOI治疗。低风险组的总生存期比高风险组好（P <0.0001），并且1年，3年和5年总生存期的AUC分别为0.582、0.634和0.636。八个小分子试剂，即XL844，AT7519，AT9283，alvocidib，nelarabine，苯甲idine，L-谷氨酰胺和锌被确定为控制HNSCC LOI的新候选药物（P <0.05）。两个mRNA标记（CNFN和DEPDC1）可以用作预测LOI风险的独立生物标志物，并为HNSCC中LOI的潜在机制提供新见解。此外，小分子药物似乎有望用于LOI治疗。低风险组的总生存期比高风险组好（P <0.0001），并且1年，3年和5年总生存期的AUC分别为0.582、0.634和0.636。八个小分子试剂，即XL844，AT7519，AT9283，alvocidib，nelarabine，苯甲idine，L-谷氨酰胺和锌被确定为控制HNSCC LOI的新候选药物（P <0.05）。两个mRNA标记（CNFN和DEPDC1）可以用作预测LOI风险的独立生物标志物，并为HNSCC中LOI的潜在机制提供新见解。此外，小分子药物似乎有望用于LOI治疗。Alvocidib，nelarabine，benzamidine，L-谷氨酰胺和锌被确定为控制HNSCC LOI的新候选者（P <0.05）。两个mRNA标记（CNFN和DEPDC1）可以用作预测LOI风险的独立生物标志物，并为HNSCC中LOI的潜在机制提供新见解。此外，小分子药物似乎有望用于LOI治疗。Alvocidib，nelarabine，benzamidine，L-谷氨酰胺和锌被确定为控制HNSCC LOI的新候选药物（P <0.05）。两个mRNA签名（CNFN和DEPDC1）可以用作预测LOI风险的独立生物标志物，并为HNSCC中LOI的潜在机制提供新见解。此外，小分子药物似乎有望用于LOI治疗。