侵袭性肿瘤前部肿瘤细胞中高表达的NELFE是口腔鳞状细胞癌的预后生物标志物。

IF 2.3 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Yizhuo Xue, Lingyun Liu, Liyuan Yu, Zihui Li, Xiaofeng Huang, Sheng Chen, Yue Jing, Xiaoxin Zhang, Liang Ding, Yuxian Song, Zhiyong Wang, Yanhong Ni
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引用次数: 0

摘要

背景:负伸长因子E (NELFE)是NELFE复合体的一个重要亚基,在转录调控和细胞命运中起着关键作用。尽管失调的NELFE在促进某些肿瘤的发生和发展中起作用,但其在口腔鳞状细胞癌(OSCC)中的表达谱、预后价值和功能仍不清楚。方法:采用免疫组化(IHC)方法分析NELFE在OSCC中的表达谱,并评价NELFE的预后价值。采用qRT-PCR和Western blot方法比较NELFE在OSCC细胞系中的表达。通过小干扰RNA片段敲低NELFE的表达,通过功能实验研究NELFE对OSCC细胞系增殖和迁移的影响。利用癌症基因组图谱(TCGA)数据进行基因集富集分析(GSEA),探讨NELFE在OSCC中的潜在机制。结果:NELFE在OSCC组织中广泛分布于肿瘤细胞(TCs)、成纤维细胞样细胞(FLCs)和肿瘤浸润淋巴细胞(TILs)。然而,与肿瘤中心成分相比,其在侵袭性肿瘤前部tc中的表达显著上调(p = 0.027)。侵袭性肿瘤前缘tc中NELFE的高表达与较高的淋巴结转移(p = 0.024)和较差的侵袭方式(p)显著相关。结论:侵袭性肿瘤前缘NELFE表达与预后不良相关,可能是OSCC潜在的预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Highly Expressed NELFE in Tumor Cells at the Invasive Tumor Front Was a Prognostic Biomarker for Oral Squamous Cell Carcinoma

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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来源期刊
CiteScore
5.90
自引率
6.10%
发文量
121
审稿时长
4-8 weeks
期刊介绍: The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry.
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