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二肽基肽酶4是甲状腺癌的潜在预后标志物及免疫治疗靶点。

DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy.

作者信息

Gao Xiaoqian, Le Yali, Geng Chenchen, Jiang Zhen, Zhao Guanghui, Zhang Ping

机构信息

Department of Ultrasound, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China.

Health Management Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China.

出版信息

Int J Endocrinol. 2022 Nov 24;2022:5181386. doi: 10.1155/2022/5181386. eCollection 2022.

Abstract

DPP4 (dipeptidyl peptidase 4) is expressed in many cancers, but the relationship between DPP4 and thyroid carcinoma (THCA) is incompletely understood. We aim to explore the expression of DPP4 in THCA and the correlation between DPP4 expression with the prognosis of THCA and antitumor immunity. We systematically analyzed data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases and explored DPP4 expression, its impact on prognosis, and its relationship with antitumor immunity in THCA. Next, we collected 18 pairs of fresh THCA and adjacent paracancerous tissues and performed RT-qPCR to validate the DPP4 mRNA level. Concurrently, immunohistochemistry (IHC) analysis was performed on 12 pairs of paraffin-embedded tissues of medullary thyroid carcinoma (MTC) and paracancerous tissues to validate the DPP4 protein level. Bioinformatics analysis showed that DPP4 mRNA expression in THCA was significantly higher than that in paracancerous tissues ( < 0.01). DPP4 was expressed at the highest levels in MTC than in other pathological types. The DPP4 expression level was different between groups with different clinical characteristics. The higher the DPP4 expressed in THCA, the lower the disease-free survival (DFS) was (HR = 1.8, =0.048). DPP4 was significantly correlated with immune cell infiltration and immune response and was positively associated with 21 immune checkpoint genes (ICGs) in THCA ( < 0.05). The results of RT-qPCR showed that the relative mRNA expression of DPP4 was significantly upregulated in 18 THCA tissues compared to that in paracancerous tissues (=0.011). IHC results showed that the DPP4 protein level was higher in 12 MTC tissues than in paracancerous tissues (=0.011). In conclusion, DPP4 is a potential prognostic marker of THCA and may become an effective target for immunotherapy.

摘要

二肽基肽酶4(DPP4)在多种癌症中均有表达,但DPP4与甲状腺癌(THCA)之间的关系尚未完全明确。我们旨在探究DPP4在THCA中的表达情况,以及DPP4表达与THCA预后和抗肿瘤免疫之间的相关性。我们系统分析了来自癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和基因表达综合数据库(GEO)的数据,探讨了DPP4在THCA中的表达、其对预后的影响以及与抗肿瘤免疫的关系。接下来,我们收集了18对新鲜的THCA组织和癌旁组织,并进行逆转录定量聚合酶链反应(RT-qPCR)以验证DPP4的mRNA水平。同时,对12对甲状腺髓样癌(MTC)石蜡包埋组织及其癌旁组织进行免疫组织化学(IHC)分析,以验证DPP4蛋白水平。生物信息学分析表明,THCA中DPP4的mRNA表达显著高于癌旁组织(<0.01)。DPP4在MTC中的表达水平高于其他病理类型。不同临床特征组之间的DPP4表达水平存在差异。THCA中DPP4表达越高,无病生存期(DFS)越低(风险比=1.8,=0.048)。DPP4与免疫细胞浸润和免疫反应显著相关,并且与THCA中的21个免疫检查点基因(ICG)呈正相关(<0.05)。RT-qPCR结果显示,与癌旁组织相比,18例THCA组织中DPP4的相对mRNA表达显著上调(=0.011)。IHC结果显示,12例MTC组织中DPP4蛋白水平高于癌旁组织(=0.011)。总之,DPP4是THCA的潜在预后标志物,可能成为免疫治疗的有效靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e3/9715318/e643379effbc/IJE2022-5181386.001.jpg

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