武汉大学中南医院检验科 湖北 武汉 430071
周峻汀,女,1998—,医学硕士生,主要从事肿瘤分子与数据科学研究,E‑mail:z15927016277@163.com
杨桂,女,1971—,副主任技师,主要从事免疫学检验的临床研究,E‑mail:2932485805@qq.com
胡鑫,男,1994—,医学博士生,主要从事肿瘤分子与数据科学研究,E‑mail: tmu2018huxin@163.com
收稿:2024-12-23,
纸质出版:2025-12-25
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周峻汀,杨桂,胡鑫.SPRR1B分子在膀胱癌中的促癌作用研究[J].武汉大学学报(医学版),2025,46(12):1590-1599.
ZHOU Junting,YANG Gui,HU Xin.Exploration of the cancer promoting effect of SPRR1B in bladder cancer[J].Medical Journal of Wuhan University,2025,46(12):1590-1599.
周峻汀,杨桂,胡鑫.SPRR1B分子在膀胱癌中的促癌作用研究[J].武汉大学学报(医学版),2025,46(12):1590-1599. DOI: 10.14188/j.1671-8852.2024.1007.
ZHOU Junting,YANG Gui,HU Xin.Exploration of the cancer promoting effect of SPRR1B in bladder cancer[J].Medical Journal of Wuhan University,2025,46(12):1590-1599. DOI: 10.14188/j.1671-8852.2024.1007.
目的
2
通过生物信息学方法综合分析富含脯氨酸小蛋白(SPRR)基因家族在膀胱癌中的表达情况和临床意义,并初步分析关键分子SPRR1B的作用机制。
方法
2
首先进行SPRR家族在膀胱癌中的表达及上下游调控分析,随后探究SPRR家族表达及与膀胱癌临床病理特征之间的相关性。最后利用膀胱癌组织标本验证了SPRR1B的表达水平,并开展细胞实验验证了SPRR1B对膀胱癌细胞表型的影响。
结果
2
SPRR1B/2D/2E/2G在膀胱癌组织中的表达水平显著高于正常组织。SPRR1A/1B/2A/2D/2F/2G/3/4的DNA甲基化水平均低于癌旁正常组织。对SPRR家族及其共表达基因所构建的蛋白互作网络的功能富集分析结果表明,富集到的通路包括胞间连接、程序性细胞死亡、细胞黏附等。SPRR1B/2A/2D/2E/2F/2G/3在组织学分级恶性程度较高的肿瘤中显著高表达。在两个数据库的分析结果中,SPRR1B/2A/2B/2E/2G的高表达都与患者预后不良相关。膀胱癌可能存在两个潜在的SPRR家族基因相关分子亚型,这两个亚型的患者之间存在预后差异。SPRR1B在膀胱癌患者组织中表达显著升高,且敲低SPRR1B能够抑制膀胱癌5637细胞增殖和迁移。
结论
2
SPRR家族成员可能通过多种机制参与膀胱癌的发生发展,膀胱癌组织中SPRR1B表达明显升高,SPRR1B能促进膀胱癌5637细胞增殖和迁移。
Objective
2
To analyze the expression and clinical significance of the small proline rich protein (SPRR) gene family in bladder cancer by bioinformatics methods and explore the preliminary mechanism of the key molecule SPRR1B.
Methods
2
Firstly
the expression and regulatory networks of the SPRR family in bladder cancer were analyzed. Then
the correlation between SPRR family expression and the clinicopathological features of bladder cancer was explored. The expression level of SPRR1B in bladder cancer tissues was verified
and cell experiments confirmed the effect of SPRR1B on the phenotypic traits of bladder cancer cells.
Results
2
The expression levels of SPRR1B/2D/2E/2G in bladder cancer tissues were significantly higher than those in normal tissues. The DNA methylation levels of SPRR1A/1B/2A/2D/2F/2G/3/4 were lower than those in adjacent normal tissues. Functional enrichment analysis of the protein-protein interaction network constructed by the SPRR family and their co-expressed genes showed that the enriched pathways included intercellular junction
programmed cell death
cell adhesion
and related pathways. SPRR1B/2A/2D/2E/2F/2G/3 were highly expressed in tumors with higher histological grades. High expression of SPRR1B/2A/2B/2E/2G was associated with poor prognosis in two databases. There may be two potential molecular subtypes of bladder cancer related to SPRR family genes
and there exists a difference in prognosis between these two subtypes. The expression of SPRR1B is significantly increased in bladder cancer tissues
and SPRR1B knockdown can inhibit the proliferation and migration of bladder cancer 5637 cells.
Conclusion
2
SPRR family members may be involved in the development of bladder cancer through multiple mechanisms. SPRR1B expression was significantly increased in bladder cancer tissues
and SPRR1B promoted the proliferation and migration of the 5637 cells.
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