Department of Life Science, School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India.
National Institute of Health, Bethesda, MD, USA.
Sci Rep. 2023 Aug 28;13(1):14033. doi: 10.1038/s41598-023-41348-2.
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.
癌症是一种异常的、异质性的细胞生长，具有侵袭周围组织甚至远处器官的能力。在全球范围内，GLOBOCAN 估计 2018 年有 1810 万例新发病例和 960 万例癌症死亡病例。在所有癌症中，口腔癌（OC）是全球第六大常见癌症，在印度是第三大常见癌症，最常见的类型是口腔鳞状细胞癌（OSCC），往往在晚期扩散到淋巴结。尽管在理解口腔癌特别是淋巴结转移的基因组规模基因表达模式方面取得了突破，但在过去几十年中，OSCC 生物学的分子景观仍然未知。此外，由于在单个队列研究中组织的可变性，对 OSCC 基因表达谱的研究很少或不一致。该工作提供了对表达变化的全面分析，并主要侧重于采用液体活检基础方法来寻找新的治疗靶点和用于淋巴结转移的早期预测生物标志物。因此，目前的研究结合了 GSE9844、GSE30784、GSE3524 和 GSE2280 队列的谱信息，筛选差异表达基因，然后使用基因富集分析和蛋白质-蛋白质相互作用网络设计，确定了淋巴结转移患者中可能的候选基因和途径。此外，使用实时 PCR 评估发现基因的 mRNA 表达，并利用 Human Protein Atlas 数据库确定肿瘤和正常组织中枢纽基因的蛋白水平。使用绒毛尿囊膜 (CAM) 血管生成试验研究血管生成。在一组 OSCC 患者中，纤维连接蛋白 (FN1)、C-X-C 基元趋化因子配体 8 (CXCL8) 和基质金属蛋白酶 9 (MMP9) 显著上调，证实了这一发现。我们鉴定的显著基因特征显示，血清外泌体在早期检测中具有更高的有效性，并与建立前转移龛的细胞内通讯相关。此外，CAM 试验的结果表明，原发性 OC 衍生的外泌体可能在血管生成中发挥作用。因此，我们的研究发现了三个可能作为淋巴结转移早期检测的潜在生物标志物的基因，并揭示了导致前转移状态的外泌体的潜在过程。
