Highly Expressed NELFE in Tumor Cells at the Invasive Tumor Front Was a Prognostic Biomarker for Oral Squamous Cell Carcinoma

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BACKGROUND: Negative elongation factor E (NELFE) is a crucial subunit of the NELF complex, which plays pivotal roles in transcriptional regulation and cell fate. Despite the role of dysregulated NELFE in promoting the onset and progression of some kinds of tumors, its expression profile, prognostic value, and function in oral squamous cell carcinoma (OSCC) still remain unknown. METHODS: Immunohistochemistry (IHC) was utilized to analyze the NELFE expression profile in OSCC, and the prognostic values of NELFE were also evaluated. qRT-PCR and Western blot were used to compare the expression of NELFE in OSCC cell lines. NELFE expression was knocked down by small interfering RNA fragments, and functional experiments were conducted to investigate the impact of NELFE on the proliferation and migration of OSCC cell lines. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data to explore potential mechanisms of NELFE in OSCC. RESULTS: NELFE was widely distributed throughout tumor cells (TCs), fibroblast-like cells (FLCs), and tumor infiltrating lymphocytes (TILs) in OSCC tissue. However, its expression was significantly upregulated in TCs at the invasive tumor front compared to the tumor center components (p = 0.027). Higher expression of NELFE in TCs at the invasive tumor front (ITF) was significantly associated with higher lymph node metastasis (p = 0.024), worse invasion pattern (p < 0.0001), and more advanced tumor node metastasis classification (p = 0.002). Additionally, higher expression of NELFE in TCs at the invasive tumor front was also linked to higher recurrence (p = 0.021) and shorter disease-free (HR = 2.045, p = 0.006) as well as relapse-free survival (HR = 2.369, p = 0.011). The NELFE mRNA and protein were generally expressed in OSCC cells. Functionally, silencing NELFE significantly inhibited the proliferation and migration capabilities of OSCC tumor cells in vitro. Finally, GSEA revealed a significant difference in the E2F pathway between NELFE high and low expression. CONCLUSIONS: NELFE expression at the invasive front was associated with poor prognosis and could be a potential prognostic biomarker for OSCC.

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