母抗十二肽同源物7在头颈鳞状细胞癌的表达及其预后诊断价值

doi:10.7518/hxkq.2025.2024341

华西口腔医学杂志 ›› 2025, Vol. 43 ›› Issue (5): 660-670.doi: 10.7518/hxkq.2025.2024341

• 基础研究 • 上一篇

母抗十二肽同源物7在头颈鳞状细胞癌的表达及其预后诊断价值

赵海惠¹^,²(), 钟晓娟²^,³, 黄怡², 费伟¹^,²^,⁴()

^1.西南医科大学口腔医学院，泸州 646000
^2.四川省医学科学院·四川省人民医院口腔医学中心，成都 610072
^3.电子科技大学医学院，成都 610051
^4.四川省人民医院温江医院口腔科，成都 610203

收稿日期:2024-09-12 修回日期:2025-04-08 出版日期:2025-10-01 发布日期:2025-10-21
通讯作者: 费伟 E-mail:1359218756@qq.com;fwross10@sina.com
作者简介:赵海惠，硕士，E-mail：1359218756@qq.com
基金资助:
四川省医学科学院·四川省人民医院院科研基金(20-21LZ01)

Expression and prognostic value of mothers against decapentaplegic homolog 7 in head and neck squamous cell carcinoma

Zhao Haihui¹^,²(), Zhong Xiaojuan²^,³, Huang Yi², Fei Wei¹^,²^,⁴()

^1.School of Stomatology, Southwest Medical University, Luzhou 646000, China
^2.Oral Medicine Center, Sichuan Provincial Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, China
^3.School of Medicine, University of Electronic Science and Technology, Chengdu 610051, China
^4.Dept. of Stomatology, Wenjiang Hospital of Sichuan Provincial People’s Hospital, Chengdu 610203, China

Received:2024-09-12 Revised:2025-04-08 Online:2025-10-01 Published:2025-10-21
Contact: Fei Wei E-mail:1359218756@qq.com;fwross10@sina.com
Supported by:
The Scientific Research Foundation of Sichuan Provincial Academy of Medical Sciences & Sichuan Provincial People’s Hospital(2021LZ01)

摘要/Abstract

摘要：

目的通过生物信息学分析及基础实验探究母抗十二肽同源物（SMAD）7对头颈鳞状细胞癌（HNSCC）的生物学功能及临床价值。方法在公开数据库中研究SMAD7在HNSCC中的表达，Western blot检测HNSCC细胞系与正常上皮细胞中SMAD7的表达；沉默SMAD7高表达的HNSCC细胞系HSC-4，分别进行CCK-8、Transwell实验、细胞划痕等实验研究SMAD7对HSC-4细胞生物学功能的影响；在UCSC xena中获得HNSCC表达谱数据，筛选SMAD7的相关基因，进行基因本体论、京都基因与基因组百科全书基因富集分析，构建共表达基因相互作用网络，筛选相关细胞信号通路，Western blot检测沉默SMAD7的HNSCC细胞中的相关细胞信号通路蛋白的表达变化；利用cBioPortal分析SMAD7基因突变率、运用MethSurv数据库分析SMAD7基因甲基化水平及其与预后水平的关系，受试者工作特征曲线评估SMAD7对HNSCC的诊断价值；TIMER2.0分析SMAD7表达与免疫细胞浸润相关性。结果 SMAD7在HNSCC肿瘤组织及部分细胞系中高度表达。沉默SMAD7表达可显著抑制癌症细胞的增殖、迁移和侵袭。沉默SMAD7可诱导血管细胞黏附分子1（VCAM-1）的下调。通过生物信息学分析，SMAD7的基因突变率和基因甲基化水平与HNSCC患者的预后显著相关。此外，SMAD7的表达与HNSCC中的免疫细胞浸润水平有关。结论 SMAD7通过调节VCAM-1表达促进HNSCC细胞增殖、迁移和侵袭，可能是HNSCC潜在的肿瘤生物标志物和治疗靶点。

关键词: 母抗十二肽同源物7, 头颈鳞状细胞癌, 血管细胞黏附分子1, 诊断, 免疫治疗

Abstract:

Objective This study aimed to explore the biological functions and clinical value of mothers against decapentaplegic homolog (SMAD) 7 in head and neck squamous cell carcinoma (HNSCC) through bioinformatics analysis and basic experiments. Methods The expression of SMAD7 in HNSCC in public databases was studied. Western blot was used to detect the expression of SMAD7 in HNSCC cell lines and normal epithelial cells. The SMAD7 highly expressed HNSCC cell line HSC-4 was silenced, and CCK-8, Transwell assays, and cell scratch experiments were conducted to study the effect of SMAD7 on the biological functions of HSC-4 cells. HNSCC expression profile data were obtained from UCSC xena, and genes related to SMAD7 were selected for gene ontology and Kyoto encyclopedia of genes and genomes gene enrichment analysis, construction of a co-expression gene interaction network, and screening of related cell signaling pathways. Western blot was used to detect the expression changes of proteins in the related cell signaling pathways in HNSCC cells with silenced SMAD7. cBioPortal was utilized to analyze the mutation rate of the SMAD7 gene, and the MethSurv database was used to analyze the methylation level of the SMAD7 gene and its correlation with prognosis. The receiver operating characteristic curve was used to assess the diagnostic value of SMAD7 for HNSCC. TIMER2.0 was used to analyze the correlation between SMAD7 expression and immune cell infiltration. Results SMAD7 was highly expressed in HNSCC tumor tissues and some cell lines. Silencing the expression of SMAD7 can significantly inhibit the proliferation, migration, and invasion of cancer cells. Silencing SMAD7 can induce the downregulation of vascular cell adhesion molecule 1 (VCAM-1). The bioinformatics analysis showed that the mutation rate of the SMAD7 gene and the methylation level were significantly correlated with the prognosis of patients with HNSCC. The expression of SMAD7 was related to the level of immune cell infiltration in HNSCC. Conclusion SMAD7 promotes the proliferation, migration, and invasion of HNSCC cells by regulating the expression of VCAM-1. It may be a potential tumor biomarker and therapeutic target for HNSCC.

Key words: mothers against decapentaplegic homolog 7, head and neck squamous cell carcinoma, vascular cell adhesion molecule 1, diagnosis, immunotherapy

中图分类号:

R739.8

赵海惠, 钟晓娟, 黄怡, 费伟. 母抗十二肽同源物7在头颈鳞状细胞癌的表达及其预后诊断价值[J]. 华西口腔医学杂志, 2025, 43(5): 660-670.

Zhao Haihui, Zhong Xiaojuan, Huang Yi, Fei Wei. Expression and prognostic value of mothers against decapentaplegic homolog 7 in head and neck squamous cell carcinoma[J]. West China Journal of Stomatology, 2025, 43(5): 660-670.

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参考文献 36

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临床病理特征		例数
年龄/岁	≥60	344
	<60	267
	未报道	1
性别	男	444
	女	168
饮酒史	无	197
	有	401
	未报道	14
抽烟史	无	255
	有	357
病理T分期	0	1
	1	52
	2	167
	3	122
	4	208
	未报道	62
临床分期	Ⅰ	23
	Ⅱ	120
	Ⅲ	137
	Ⅳ	318
	未报道	14
病理上淋巴结转移	无	206
	有	290
	未报道	116

慢病毒载体	靶点序列
control	5’-GCTTCGCGCCGTAGTCTTA-3’
sh1	5’-GGATATCTTCTATGATCTACC-3’
sh2	5’-GCCGAACCAGAACCAATTATT-3’
sh3	5’-GCTCAATGAGCATGTTTAGAC-3’

母抗十二肽同源物7在头颈鳞状细胞癌的表达及其预后诊断价值

Expression and prognostic value of mothers against decapentaplegic homolog 7 in head and neck squamous cell carcinoma

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