NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma

Abstract

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.

Anatomical landscape of oral squamous cell carcinoma: A single cancer center study in UAE

“…In addition to investigating the clinicopathological variation across the different anatomical subsites, it was also prudent to investigate the oncogenes that drive carcinogenesis and have the potential to be employed as prognostic variables and therapeutic targets. Recent advances in high-throughput multi-omic technologies have enabled full molecular profiling of tumor samples to discover drivers of oncogenesis and progression, which may lead to the development of targeted oncotherapeutics which influence prognosis and survival of oral cancer at different anatomical subsites [ 30 ]. For example, NCBP2 and TFRC expression had been recently associated with increased mortality in patients with OSCC, with targeted NCBP2 depletion showing promising results as a novel oncotherapy for the suppression cell migration, invasion, and proliferation [ 30 ].…”

“…Recent advances in high-throughput multi-omic technologies have enabled full molecular profiling of tumor samples to discover drivers of oncogenesis and progression, which may lead to the development of targeted oncotherapeutics which influence prognosis and survival of oral cancer at different anatomical subsites [ 30 ]. For example, NCBP2 and TFRC expression had been recently associated with increased mortality in patients with OSCC, with targeted NCBP2 depletion showing promising results as a novel oncotherapy for the suppression cell migration, invasion, and proliferation [ 30 ]. Furthermore, the recent identification of SERPINH1 as a protein with notable cell-surface expression in the oncogenesis of head-and-neck-SCCs has aided the development of a novel photothermal assisted targeted oncotherapy via gold nanostars combined with the searched SERPINH1 antibody; thereby illustrating the potential of key genes as biomarkers and therapeutic targets for OSCC [ 31 ].…”

The m7G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling

“…As a CBC, NCBP2 could recognize the m 7 G "cap" on RNA and promote RNA maturation, transportation, and translation in conjunction with eIF4E [18,[33][34][35][58][59][60][61][62]. Moreover, several studies have indicated that NCBP2 promotes the proliferation, metastasis, and immune escape of oral squamous cell carcinoma and head and neck squamous cell carcinoma [63,64]. Consistent with these findings, we identified that NCBP2 promotes PDAC progression by upregulating c-JUN-mediated MEK/ERK signaling activation in an m 7 G methylation-dependent manner.…”