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分析头颈鳞状细胞癌中的肌球蛋白基因,并鉴定 MYL1 作为一个特定的不良预后生物标志物,促进头颈鳞状细胞癌中的肿瘤转移,并与肿瘤免疫浸润相关。

Analysis of myosin genes in HNSCC and identify MYL1 as a specific poor prognostic biomarker, promotes tumor metastasis and correlates with tumor immune infiltration in HNSCC.

机构信息

Department of Otorhinolaryngology, Qilu Hospital, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, China.

出版信息

BMC Cancer. 2023 Sep 7;23(1):840. doi: 10.1186/s12885-023-11349-5.

Abstract

Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.

摘要

头颈部鳞状细胞癌(HNSCC)是最常见的恶性肿瘤之一,全球发病率排名第六。尽管近年来 HNSCC 的治疗方法有了显著改善,但复发率和死亡率仍然很高。肌球蛋白基因在多种肿瘤中得到了研究,但在 HNSCC 中的作用尚未阐明。本研究通过 GSE58911 和 GSE30784 基因表达谱分析检测 HNSCC 中显著失调的肌球蛋白基因。使用癌症基因组图谱(TCGA)HNSCC 数据库验证失调的肌球蛋白基因,并研究这些基因与 HNSCC 预后的关系。结果显示,MYL1、MYL2、MYL3、MYH2 和 MYH7 在 HNSCC 患者中下调,而 MYH10 上调。有趣的是,MYL1、MYL2、MYH1、MYH2 和 MYH7 被证明是 HNSCC 的不利预后标志物。值得注意的是,MYL1 是 HNSCC 中一种特异性的不利预后生物标志物。MYL1、MYL2、MYL3、MYH2、MYH7 和 MYH10 促进 HNSCC 中 CD4+T 细胞的激活。MYL1 在蛋白质水平上被证明在 HNSCC 组织中低于正常组织。MYL1 过表达对增殖没有影响,但显著促进了 Fadu 细胞的迁移。MYL1 增加了 EGF 和 EGFR 蛋白表达水平。此外,在 HNSCC 中,MYL1 表达与 Tcm CD8 细胞、Tcm CD4+细胞、NK 细胞、肥大细胞、NKT 细胞、Tfh 细胞和 Treg 细胞呈正相关。总的来说,MYL1 促进肿瘤转移,并与 HNSCC 中的肿瘤免疫浸润相关,这些作用可能与 EGF/EGFR 途径有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a0b/10486092/d37a435f09f8/12885_2023_11349_Fig1_HTML.jpg

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