"CCNB1 is a novel prognostic biomarker and promotes proliferation, migration and invasion in Wilms tumor"

作者全名："Xiang, Bin; Chen, Mei-Lin; Gao, Zhi-Qiang; Mi, Tao; Shi, Qin-Lin; Dong, Jun-Jun; Tian, Xiao-Mao; Liu, Feng; Wei, Guang-Hui"

作者地址："[Xiang, Bin; Chen, Mei-Lin; Gao, Zhi-Qiang; Mi, Tao; Shi, Qin-Lin; Dong, Jun-Jun; Tian, Xiao-Mao; Liu, Feng; Wei, Guang-Hui] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Int Sci, Chongqing, Peoples R China; [Xiang, Bin; Chen, Mei-Lin; Gao, Zhi-Qiang; Mi, Tao; Shi, Qin-Lin; Dong, Jun-Jun; Tian, Xiao-Mao; Liu, Feng; Wei, Guang-Hui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China"

通信作者："Tian, XM; Liu, F (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Int Sci, Chongqing, Peoples R China.; Tian, XM; Liu, F (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China."

来源：BMC MEDICAL GENOMICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001049473000001

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：16

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：RNA sequencing; Wilms tumor; CCNB1; Prognoses; Nomogram; Immune infiltration

摘要："BackgroundWilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies.MethodsHigh-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments.ResultsWe initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with 'cell cycle', 'DNA replication'. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients' overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays.ConclusionOur study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target."

基金机构：　

基金资助正文：