背景:先前的几项研究表明,cullin(CUL)家族蛋白的差异表达可能参与与癌症相关的信号转导途径的介导。然而,CULs在头颈部鳞状细胞癌(HNSCC)中的功能尚不清楚。
方法:我们使用了癌症基因组图谱(TCGA)数据库,cBioPortal,Metascape,STRING,Cytoscape,肿瘤免疫评估资源(TIMER),卡普兰-迈耶绘图仪,和肿瘤免疫系统相互作用数据库(TISIDB)来获取CULs的表达以及与肿瘤发生的可能相关性,发展,预后,豁免权,和HNSCC中CULs的转录水平。此外,实时定量聚合酶链反应(RT-qPCR)用于检测HNSCC组织和细胞样品中的信使核糖核酸(mRNA)水平。我们还通过CCK8测定和伤口愈合测定分别探索了细胞增殖和迁移。
结果:结果显示,与正常患者相比,HNSCC患者中CUL2/4A的表达上调,CUL9的表达下调。在生物信息学分析中,CUL2/4A/9也与HNSCC的临床病理特征和总体生存率相关。此外,我们注意到CUL2/4A/9可能通过调节肿瘤浸润淋巴细胞(TIL)和免疫调节剂参与肿瘤特异性免疫反应。最后,我们发现CUL2/4A/9可以促进细胞增殖和迁移。
结论:这些结果表明CUL2/4A/9的转录水平上调,这些基因可能影响HNSCC细胞的增殖和迁移。因此,CUL2/4A/9可能作为HNSCC患者的新型独立生物标志物发挥作用。
BACKGROUND: Several previous studies have shown that differential expression of
cullin (CUL) family proteins may be involved in mediation of the signal transduction pathways associated with cancer. However, the function of CULs is still unclear in head and neck squamous cell carcinoma (HNSCC).
METHODS: We used The Cancer Genome Atlas (TCGA) database, cBioPortal, Metascape, STRING, Cytoscape, Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter, and Tumor Immune System Interaction Database (TISIDB) to access the expression of CULs and the possible correlation with the tumourigenesis, development, prognosis, immunity, and transcriptional level of CULs in HNSCC. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect messenger ribonucleid acid (mRNA) levels in HNSCC tissues and cell samples. We also explored the cell proliferation and migration separately by CCK8 assay and wound healing assay.
RESULTS: The results showed that the expressions of CUL2/4A were upregulated and CUL9 was downregulated in HNSCC patients as compared with normal patients. CUL2/4A/9 were also linked to the clinicopathological features and overall survival of HNSCC in bioinformatics analysis. Moreover, we noticed that CUL2/4A/9 may take part in tumour-specific immune response by modulating the tumour-infiltrating lymphocytes (TILs) and immunomodulators. Lastly, we found that CUL2/4A/9 could promote cellular proliferation and migration.
CONCLUSIONS: These results suggest that the transcriptional levels of CUL2/4A/9 were upregulated and these genes could affect proliferation and migration of HNSCC cells. Therefore, CUL2/4A/9 could potentially function as novel independent biomarkers in HNSCC patients.