癌症是细胞异常、异质性生长的疾病，具有侵袭周围组织甚至远处器官的能力。根据全球癌症统计（GLOBOCAN）的数据，2018年全球癌症新病例约为1810万，死亡率为960万。在所有癌症中，口腔癌（OC）是全球第六常见的癌症，也是印度第三常见的癌症，其中最常见类型口腔鳞状细胞癌（OSCC）在晚期阶段往往会向淋巴结扩散。然而，在过去几十年中，尽管我们对于口腔癌，特别是淋巴结转移方面的基因组规模基因表达模式的理解取得了突破，但OSCC的分子景观仍然未知。此外，由于单一队列研究中组织的变异性，关于OSCC基因表达谱的研究非常有限且不一致。本研究对变化的表达进行了全面分析，并重点采用液体活检基础方法寻找淋巴结转移的新治疗靶点和早期预测生物标志物。因此，本研究结合了GSE9844、GSE30784、GSE3524和GSE2280队列的概况信息，筛选出差异表达基因，然后利用基因富集分析和蛋白质相互作用网络设计，鉴定了淋巴结转移患者可能的候选基因和通路。此外，采用实时聚合酶链反应评估发现的基因的mRNA表达，并利用人类蛋白质图谱数据库确定瘤组织和正常组织中关键基因的蛋白质水平。通过Corioallentoic膜（CAM）血管生成实验探究了血管生成情况。在一组OSCC患者中，纤维连接蛋白（FN1）、C-X-C趋化因子配体8（CXCL8）和基质金属蛋白酶9（MMP9）的表达显著上调，证实了这些发现。我们鉴定的显著基因签名表明血清外泌体在早期检测方面具有更高的效力，并与前转移巢穴的细胞间通讯临床相关。此外，CAM实验结果显示原发性OC来源的外泌体可能在血管生成中起作用。因此，本研究发现了三个潜在基因，可作为淋巴结转移早期检测的潜在生物标志物，并揭示了导致前转移状态的外泌体潜在机制。© 2023 Springer Nature Limited.

Cancer is an abnormal, heterogeneous growth of cells with the ability to invade surrounding tissue and even distant organs. Worldwide, GLOBOCAN had an estimated 18.1 million new cases and 9.6 million death rates of cancer in 2018. Among all cancers, Oral cancer (OC) is the sixth most common cancer worldwide, and the third most common in India, the most frequent type, oral squamous cell carcinoma (OSCC), tends to spread to lymph nodes in advanced stages. Throughout the past few decades, the molecular landscape of OSCC biology has remained unknown despite breakthroughs in our understanding of the genome-scale gene expression pattern of oral cancer particularly in lymph node metastasis. Moreover, due to tissue variability in single-cohort studies, investigations on OSCC gene-expression profiles are scarce or inconsistent. The work provides a comprehensive analysis of changed expression and lays a major focus on employing a liquid biopsy base method to find new therapeutic targets and early prediction biomarkers for lymph node metastasis. Therefore, the current study combined the profile information from GSE9844, GSE30784, GSE3524, and GSE2280 cohorts to screen for differentially expressed genes, and then using gene enrichment analysis and protein-protein interaction network design, identified the possible candidate genes and pathways in lymph node metastatic patients. Additionally, the mRNA expression of discovered genes was assessed using real-time PCR, and the Human Protein Atlas database was utilized to determine the protein levels of hub genes in tumor and normal tissues. Angiogenesis was been investigated using the Chorioallentoic membrane (CAM) angiogenesis test. In a cohort of OSCC patients, fibronectin (FN1), C-X-C Motif Chemokine Ligand 8 (CXCL8), and matrix metallopeptidase 9 (MMP9) were significantly upregulated, corroborating these findings. Our identified significant gene signature showed greater serum exosome effectiveness in early detection and clinically linked with intracellular communication in the establishment of the premetastatic niche. Also, the results of the CAM test reveal that primary OC derived exosomes may have a function in angiogenesis. As a result, our study finds three potential genes that may be used as a possible biomarker for lymph node metastasis early detection and sheds light on the underlying processes of exosomes that cause a premetastatic condition.© 2023. Springer Nature Limited.