当前在口腔鳞状细胞癌（OSCC）的临床管理中，预后生物标志物和靶向治疗方法都很少，患者的预后仍然很差。在OSCC的大多数突变中，是肿瘤抑制基因功能缺失事件，很难用传统方式进行靶向。有趣的是，在许多上皮性癌症中，包括OSCC，染色体片段3q22-3q29存在扩增。我们猜想位于3q22-3q29的468个基因中，有些可能是口腔癌发生的驱动因素，可以作为潜在的预后生物标志物和治疗靶点。通过对The Cancer Genome Atlas（TCGA）的拷贝数变异（CNV）、基因表达和临床数据进行综合分析，我们确定了两个候选基因：NCBP2、TFRC，它们的表达与HPV阴性OSCC患者的整体生存（OS）呈正相关。与大多数正常人组织相比，NCBP2和TFRC在肿瘤细胞中的表达显著更高。高水平的NCBP2和TFRC蛋白丰度与HPV阴性OSCC患者的整体、疾病特异性生存和无进展生存时间的恶化有关。最后，由于缺乏NCBP2在癌症发生中的证据，我们测试了调节人类OSCC细胞系中NCBP2水平是否影响其致癌行为。我们发现，NCBP2缺乏会降低OSCC细胞的增殖、迁移和侵袭能力。差异表达分析揭示了高NCBP2表达患者中多种肿瘤促进基因的上调。因此，我们提出NCBP2和TFRC均可以作为新的预后生物标志物和潜在治疗靶点，用于HPV阴性OSCC的治疗。©2023作者。

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.© 2023. The Author(s).