Affiliated Zhongda Hospital of Southeast University, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, China.
Binhai People's Hospital, Yancheng, China.
Gene. 2022 Jul 20;832:146514. doi: 10.1016/j.gene.2022.146514. Epub 2022 May 9.
Sunitinib is a first-line drug in the treatment of metastatic renal cell carcinoma, but patients will inevitably develop drug resistance after 6-15 months of systematic treatment, which seriously affects the prognosis in KIRC.
During the study, the Gene Expression Omnibus (GEO) database was used to perform a systematic bioinformatics analysis,so that we could determine the genes (DEGs) which are differentially expressed between sunitinib-sensitive and sunitinib-resistant RCC (SRRC) cells.
A total of 31 DEGs were identified. Gene ontology (GO) was used to analyze the function of DEGS. These DEGs were found mainly enriched in organic aniontransmembrane transporter. The Cytohubba plug-in, STRING database and Cytoscape software were involved to construct a protein-protein interaction (PPI) network, and the pivot genes were identified by single-gene and multi-gene Cox regression analysis. Finally, DDX58 and MX2 were identified as prognostic genes. Survival analysis was performed by using prognostic nomogram, prognostic histogram and GEPIA database to verify the relationship between DDX58 and MX2 expression and survival. The relationship between the two pivot genes and the prognosis of patients was further verified by using the KM survival analyses and Time Dependency ROC curve analyses from TCGA database. Immunohistochemical analyses confirmed that, in tumor tissues and normal tissues, DDX58 and MX2 were differentially expressed. The expression of these two genes have relationship with the immune checkpoint.
This study provides insights into the molecular mechanisms of SRRC, as well as the selection of therapeutic and prognostic biomarkers for SRRC.
舒尼替尼是转移性肾细胞癌（KIRC）一线治疗药物，但患者在接受 6-15 个月的系统治疗后不可避免地会产生耐药性，严重影响 KIRC 的预后。
本研究通过基因表达综合数据库（GEO）进行系统生物信息学分析，确定舒尼替尼敏感和耐药肾透明细胞癌（SRRC）细胞之间差异表达的基因（DEGs）。
共鉴定出 31 个 DEGs。通过基因本体论（GO）分析 DEGs 的功能，这些 DEGs 主要富集在有机阴离子跨膜转运体。通过 Cytohubba 插件、STRING 数据库和 Cytoscape 软件构建蛋白质-蛋白质相互作用（PPI）网络，通过单基因和多基因 Cox 回归分析确定枢纽基因。最后，鉴定出 DDX58 和 MX2 为预后基因。通过预后列线图、预后直方图和 GEPIA 数据库进行生存分析，验证 DDX58 和 MX2 表达与生存的关系。进一步通过 TCGA 数据库的 KM 生存分析和时间依赖性 ROC 曲线分析验证这两个枢纽基因与患者预后的关系。免疫组织化学分析证实，在肿瘤组织和正常组织中，DDX58 和 MX2 的表达存在差异。这两个基因的表达与免疫检查点有关。
本研究为 SRRC 的分子机制以及 SRRC 治疗和预后生物标志物的选择提供了新的见解。
