Li Jian, Sun Ruili, He Lixiang, Sui Guoyi, Di Wenyu, Yu Jian, Su Wei, Pan Zenggang, Zhang Yu, Zhang Jinghang, Ren Feng
Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University Xinxiang 453003, Henan, China.
Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University Xinxiang 453003, Henan, China.
Am J Transl Res. 2022 Jun 15;14(6):3750-3768. eCollection 2022.
Despite recent research highlighting the critical function of RIO kinase 3 (RIOK3) in a variety of malignancies, a comprehensive evaluation of RIOK3 in human tumors is absent. Our study helps to clarify the molecular mechanism of RIOK3 in carcinogenesis from multiple perspectives.
Our research looked into the potential oncogenic role of RIOK3 in 33 cancers using TCGA (The Cancer Genome Atlas), GTEx (Genotype-Tissue Expression Project), GEO (Gene Expression Omnibus) datasets, and several bioinformatics tools.
RIOK3 expression in tumors is disordered compared to normal tissue, and it is highly linked with the level of MMR (Mismatch repair) gene mutations and DNA methyltransferase expression. According to univariate survival analysis, it could be used as an independent prognostic factor. Further investigation demonstrated that RIOK3 expression was correlated with cancer-associated fibroblast, neutrophil, and endothelial infiltration levels in kidney cancer and was positively correlated with the expression of immune checkpoint markers in different cancers. The functional pathways of RIOK3 also included cell-cell adhesion, protein phosphorylation, and innate immune-related functions.
These findings suggest that RIOK3 could be used as an immunological and prognostic biomarker in various malignant tumors.
尽管最近的研究强调了RIO激酶3(RIOK3)在多种恶性肿瘤中的关键作用,但目前缺乏对RIOK3在人类肿瘤中的全面评估。我们的研究有助于从多个角度阐明RIOK3在致癌过程中的分子机制。
我们的研究利用TCGA(癌症基因组图谱)、GTEx(基因型-组织表达项目)、GEO(基因表达综合数据库)数据集以及多种生物信息学工具,探究了RIOK3在33种癌症中的潜在致癌作用。
与正常组织相比,肿瘤中RIOK3的表达紊乱,并且它与错配修复(MMR)基因突变水平和DNA甲基转移酶表达高度相关。根据单因素生存分析,它可作为一个独立的预后因素。进一步研究表明,RIOK3的表达与肾癌中癌症相关成纤维细胞、中性粒细胞和内皮细胞浸润水平相关,并且在不同癌症中与免疫检查点标志物的表达呈正相关。RIOK3的功能途径还包括细胞间粘附、蛋白质磷酸化和先天免疫相关功能。
这些发现表明,RIOK3可作为多种恶性肿瘤的免疫和预后生物标志物。