TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.
TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.
复制标题
DOI：
10.1016/j.lfs.2019.117171
复制
发表时间：
2019-12
期刊：
影响因子：
6.1
通讯作者：
Zhaoxu Xu;H. Tang;Tianshu Zhang;mingli Sun;Q. Han;Jiao Xu;M. Wei;Zhaojin Yu
中科院分区：
文献类型：
--
作者：
Zhaoxu Xu;H. Tang;Tianshu Zhang;mingli Sun;Q. Han;Jiao Xu;M. Wei;Zhaojin Yu
目的睾丸表达蛋白19（TEX 19）是近年来发现的肿瘤/睾丸抗原之一，与多种肿瘤的发生和发展有关。本研究旨在揭示TEX 19在卵巢癌中的作用，寻找TEX 19的候选表位肽，为临床应用提供依据。评估TEX 19水平与患者临床病理特征的相关性。利用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分析来检测卵巢细胞系和TEX 19缺陷细胞中的TEX 19水平。通过小干扰RNA（siRNA）敲低OVCAR-3和A2780中的TEX 19水平，并使用功能丧失测定来确定TEX 19对OC细胞的增殖、迁移和侵袭的生物学效应。通过IEDB数据库、pepsite 2网站、莫伊软件和T2细胞结合试验对TEX 19的候选表位进行预测和验证，发现TEX 19在OC中表达上调，并与肿瘤的TNM分期、淋巴结转移和侵袭性相关。TEX 19的敲低抑制OC细胞的增殖、迁移和侵袭。另外，我们还筛选了TEX 19的4个多肽，发现TL是与HLA-A* 0201亲和力最强的优势多肽。研究结果表明，TEX 19对OC具有促癌作用，TL有望成为OC的抗肿瘤表位疫苗，提示TEX 19是一个很有前途的OC生物标志物和免疫靶点。
AimsTestis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application.Main methodsTEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay.Key findingsTEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201.SignificanceOur data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.