首页|A激酶相互作用蛋白1和瞬时受体电位通道1在舌鳞状细胞癌中的临床意义及其机制

A激酶相互作用蛋白1和瞬时受体电位通道1在舌鳞状细胞癌中的临床意义及其机制

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[目的]探讨A激酶相互作用蛋白1(A kinase interacting protein 1,AKIP1)和瞬时受体电位通道1(transient receptor potential channel 1,TRPC1)在舌鳞状细胞癌(tongue squamous cell carcinoma,TSCC)中的临床意义及影响TSCC的潜在机制.[方法]筛选2016年1月至2019年12月接受手术切除联合或不联合辅助放疗的TSCC患者194例,采用免疫组化染色和RT-qPCR进行TRPC1和AKIP1蛋白和mRNA的检测,根据表达情况分为高低表达组.通过String网站筛选与AKIP1、TRPC1蛋白相互作用的蛋白,将其导入Cy-toscape软件并利用cytoHubba模块MCC法筛选出与AKIP1、TRPC1蛋白显著相关的蛋白,构建互作图;再利用KEGG rest API对密切相关的蛋白进行功能富集分析.[结果]TRPC和AKIP1在TSCC癌组织和癌旁组织的阳性表达率分别为59.8%、56.2%和40.2%、33.5%;TRPC1 mRNA和AKIP1 mRNA水平在癌组织和癌旁组织的平均值分别为2.3±1.3、2.3±1.1和1.4±0.9、1.1±0.4,高表达率分别为57.2%、50.5%和30.9%、33.5%,差异均有统计学意义(P<0.05).TRPC1蛋白和mRNA表达,在不同N分期和TNM分期患者中差异均有统计学意义(P<0.05).AKIP1蛋白表达,在不同N分期和TNM分期患者中差异有统计学意义(P<0.05),AKIP1 mRNA表达,在不同N分期、TNM分期和病理分级患者中差异均有统计学意义(P<0.05).Pearson相关性分析显示,TRPC1和AKIP1蛋白表达呈正相关,TRPC1 mRNA和AKIP1 mRNA表达也呈正相关(P<0.05).高表达TRPC1和AKIP1的患者生存期明显劣于低表达患者(P<0.05).采用String网站和Cytoscape软件筛选出与TRPC1和AKIP1密切相关基因21个,并经KEGG富集分析,结果显示这些基因主要富集于血小板激活、钙信号通路、TRP信号通路的炎性调控、Rap1信号通路、cAMP-PKG信号通路、VEGF信号通路等.[结论]TRPC1、AKIP1高表达与TSCC预后差相关,两者可能通过Rap1、VEGF等信号通路的激活进而参与肿瘤的进展.
Expression of A Kinase Interacting Protein 1 and Transient Receptor Potential Channel 1 in Patients with Tongue Squamous Cell Carcinoma and Their Clinical Significance
[Objective]To explore the expression and clinical significance of A kinase interacting protein 1(AKIP1)and transient receptor potential channel 1(TRPC1)in patients with tongue squamous cell carcinoma(TSCC).[Methods]One hundred and ninety-four TSCC patients who underwent surgical resection with or without adjuvant radiotherapy from January 2016 to December 2019 were enrolled.The expressions of TRPC1 and AKIP1 protein and mRNA were detected by immunohistochemical staining and RT-qPCR,respectively,and patients were divid-ed into high and low expression groups.The proteins interacting with TRPC1 and AKIP1 were screened on String website,and selected by MCC methods of cytoHubba module in Cytoscape,to establish an interaction diagram.KEGG rest API was applied for functional enrichment analysis of closely related proteins.[Results]The positive rate of TRPC1 and AKIP1was 59.8%,56.2%in tumor tissues and 40.2%,33.5%in adjacent tissues of TSCC(P<0.05),respectively.The mean values of TRPC1 and AKIP1mRNA in tumor and adjacent tissues were 2.3± 1.3,2.3±1.1 and 1.4±0.9,1.1±0.4,respectively;and the expression rates in tumor tissues were significantly higher than those in adjacent tissues(57.2% vs 50.5%and 30.9% vs 33.5%,P<0.05).The expression of TRPC1 protein and mRNA showed statistical differences in patients with different N stages and TNM stages(P<0.05).The expression of AKIP1 protein showed statistical significance in patients with different N stages and TNM stages(P<0.05),while the expression of AKIP1 mRNA showed statistical significance in patients with different N stages,TNM stages,and pathological grading(P<0.05).Pearson correlation analysis showed that TRPC1 protein and mRNA were positively correlated with AKIP1 protein and mRNA,respectively(P<0.05).The survival of patients with high expression of TRPC1 and AKIP1 was significantly worse than that of patients with low expression(P<0.05).Twenty one genes closely related to TRPC1 and AKIP1were screened ot by String website and Cytoscape soft-ware,KEGG enrichment analysis showed that these genes were mainly enriched in platelet activation,calcium signaling pathway,inflammatory regulation of TRP signaling pathway,Rap1 signaling pathway,cAMP-PKG sig-naling pathway and VEGF signaling pathway.[Conclusion]High expression of TRPC1 and AKIP1 is associated with poor prognosis of TSCC,they may participate in tumor progression through the activation of Rap1,VEGF and other signaling pathways.

tongue squamous cell carcinomaA kinase interacting protein 1transient receptor potential channel 1relationship analysis in proteinsKEGG signal enrichment analysis

石光、焦建军、刘英奇、张肖、杨龙龙、张晶、张学强、孙莹

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邯郸市中心医院,河北邯郸 056001

舌鳞状细胞癌 A激酶相互作用蛋白1 瞬时受体电位通道1 蛋白互作分析 KEGG通路富集分析

河北省卫生健康委员会医学科学研究课题计划项目

20231969

2024

肿瘤学杂志
浙江省肿瘤医院 浙江省抗癌协会

肿瘤学杂志

CSTPCD
影响因子:0.83
ISSN:1671-170X
年,卷(期):2024.30(2)
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