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上调的PCAT-1通过miR-145-5p/FSCN-1轴预测头颈部鳞状细胞癌的不良预后并减少免疫细胞浸润。

Upregulated PCAT-1 predicts poor prognosis and reduced immune cell infiltration in head and neck squamous cell carcinoma through the miR-145-5p / FSCN-1 axis.

作者信息

Pirhoushiaran Maryam, Heidarzadehpilehrood Roozbeh, Mokhtarinejad Mahnoosh, Hesami Sara, Rezaei Nima, Farahani Abbas Shakoori

机构信息

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran.

Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.

出版信息

Mol Biol Rep. 2025 Jan 13;52(1):121. doi: 10.1007/s11033-024-10208-1.

Abstract

BACKGROUND

LncRNA PCAT-1 is known to promote cancer proliferation, invasion, and metastasis. However, its significance in HNSCC is not fully understood. This research investigates how the PCAT-1 / miR-145-5p / FSCN-1 axis promote HNSCC.

METHODS AND RESULTS

We analyzed the gene expression patterns on 238 fresh-frozen samples, comparing tumors with their normal adjacent tissues (NATs). HNSCC samples showed higher PCAT-1 and FSCN-1 expression compared to NATs (p < 0.001 and p < 0.001, respectively). In contrast, miR-145-5p expression was markedly downregulated compared to NATs (p < 0.001). Notably, ROC curve analysis revealed exceptional diagnostic power, with an AUC of 0.83 for PCAT-1, 0.95 for miR-145-5p, and 0.91 for FSCN-1. Pearson correlation analysis unveiled a significant positive correlation between PCAT-1 and FSCN-1 expression levels (r = 0.084, p < 0.001) and negative correlations between FSCN-1 and miR-145-5p (r = -0.710, p < 0.001) as well as between PCAT-1 and miR-145-5p (r = -0.759, p < 0.001). Distinct molecular profiles were observed in the levels of PCAT-1, miR-145-5p, and FSCN-1 between HPV (-) and HPV ( +) 16 and 18 genotypes (p = 0.007, p = 0.027, and p = 0.002). MiR-145-5p expression showed significant differences between HPV (-) and HPV ( +) other genotypes (p = 0.035). FSCN-1 expression showed notable distinctions between HPV ( +) 18 & 16 and HPV ( +) other genotypes (p = 0.031).

CONCLUSIONS

Elevated levels of lncRNA PCAT-1 promote HNSCC through the miR-145-5p/FSCN-1 axis and are associated with poor prognosis and reduced immune cell infiltration levels.

摘要

背景

已知长链非编码RNA PCAT-1可促进癌症的增殖、侵袭和转移。然而,其在头颈部鳞状细胞癌(HNSCC)中的意义尚未完全明确。本研究旨在探究PCAT-1/miR-145-5p/FSCN-1轴如何促进HNSCC。

方法与结果

我们分析了238份新鲜冷冻样本的基因表达模式,将肿瘤组织与其相邻正常组织(NATs)进行比较。与NATs相比,HNSCC样本中PCAT-1和FSCN-1的表达更高(分别为p < 0.001和p < 0.001)。相比之下,与NATs相比,miR-145-5p的表达明显下调(p < 0.001)。值得注意的是,ROC曲线分析显示出卓越的诊断能力,PCAT-1的AUC为0.83,miR-1四千五百五十万分之一为0.95,FSCN-1为0.91。Pearson相关性分析揭示了PCAT-1与FSCN-1表达水平之间存在显著正相关(r = 0.084,p < 0.001),FSCN-1与miR-145-5p之间存在负相关(r = -0.710,p < 0.001),以及PCAT-1与miR-145-5p之间存在负相关(r = -0.759,p < 0.001)。在HPV(-)和HPV(+)16及18基因型之间,PCAT-1、miR-145-5p和FSCN-1的水平观察到明显不同的分子谱(p = 0.007,p = 0.027,p = 0.002)。miR-145-5p表达在HPV(-)和HPV(+)其他基因型之间存在显著差异(p = = 0.035)。FSCN-1表达在HPV(+)18和16与HPV(+)其他基因型之间存在显著差异(p = 0.031)。

结论

lncRNA PCAT-1水平升高通过miR-145-5p/FSCN-1轴促进HNSCC,并与不良预后和免疫细胞浸润水平降低相关。

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