m7G‐related genes—NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression

Abstract

Aberrant N 7 -methylguanosine (m7G) levels closely correlate with tumor genesis and progression. NCBP2 and EIF4E3 are two important m7G-related cap-binding genes.This study aimed to identify the relationship between the EIF4E3/NCBP2 function and immunological characteristics of head and neck squamous cell carcinoma (HNSCC). Hierarchical clustering was employed in classifying HNSCC patients into two groups based on the expressions of NCBP2 and EIF4E3. The differentially expressed genes were identified between the two groups, and GO functional enrichment was subsequently performed. Weighted gene co-expression network analysis was conducted to identify the hub genes related to EIF4E3/NCBP2 expression and immunity. The differential infiltration of immune cells and the response to immunotherapy were compared between the two groups. Single-cell sequence and trajectory analyses were performed to predict cell differentiation and display the expression of EIF4E3/NCBP2 in each state. In addition, quantitative real-time PCR, spatial transcriptome analysis, transwell assay, and western blotting were conducted to verify the biological function of EIF4E3/NCBP2. Here, group A showed a higher EIF4E3 expression and a lower NCBP2 expression, which had higher immune scores, proportion of most immune cells, immune activities, expression of immunomodulatory targets, and a better response to cancer immunotherapy.Besides, 56 hub molecules with notable immune regulation significance were identified. A risk model containing 17 hub genes and a prognostic nomogram was successfully established. Moreover, HNSCC tissues had a lower EIF4E3 expression and a higher NCBP2 expression than normal tissues. NCBP2 and EIF4E3 played a vital role in the differentiation of monocytes. Furthermore, the expression of CCL4/CCL5 can be regulated via EIF4E3 overexpression and NCBP2 knockdown. Collectively,

Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma

“…The efficacy of immunotherapeutic strategy relies heavily on the initial response of immune system and the presence of preexisting immunity. In the context of antitumor response, the essential contributions of CD8+ T cells and NK cells have been widely acknowledged [33] . It is important to investigate the relationship between CAFs and the infiltration of immune cells.…”

Identification and validation of N7‐methylguanosine‐associated gene NCBP1 as prognostic and immune‐associated biomarkers in breast cancer patients

“…According to one research, EIF4E3 depends on cap‐binding activity to operate as a tumour suppressor and compete with EIF4E's growth‐promoting capabilities. In fact, tumours that have increased EIF4E and low EIF4E3 expression demonstrate that EIF4E3 is of essential inhibitory mechanism that is lost in certain cancers 30 . Other investigations have shown that EIF4E3 may prevent oncogenic transformation 31–33 .…”

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

“…For example, NCBP2 and EIF4E3 can influence the immune environment and response to immunotherapy, thereby inducing tumour transformation in patients with HNSCC. 130 Another study showed that clinical adrenocortical carcinoma (ACC) patients with high METTL1 expression had lower levels of CD8+ T‐cell infiltration and higher levels of macrophage infiltration compared with those with low expression, suggesting that METTL1 exerts a profound effect on tumour immunity in ACC 131 (Figure 3 ).…”