Function and prognosis analysis of nucleolus protein DCAF13 in breast cancer

作者全名："Wang, Mei; Fu, Liang; Tian, Jun; Zhang, Yongming; Rossi, Lorenzo; Wang, Ke"

作者地址："[Wang, Mei; Tian, Jun; Zhang, Yongming; Wang, Ke] Yongchuan Peoples Hosp Chongqing, Clin Lab, Huilong Ave 375, Chongqing 402160, Peoples R China; [Fu, Liang] Chongqing Med Univ, Clin Lab, Yongchuan Hosp, Chongqing, Peoples R China; [Rossi, Lorenzo] Ente Osped Cantonale, Inst Oncol Southern Switzerland IOSI, Bellinzona, Switzerland; [Rossi, Lorenzo] Ente Osped Cantonale, Breast Unit Southern Switzerland CSSI, Lugano, Switzerland"

通信作者："Wang, K (通讯作者)，Yongchuan Peoples Hosp Chongqing, Clin Lab, Huilong Ave 375, Chongqing 402160, Peoples R China."

来源：TRANSLATIONAL CANCER RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001137364300006

JCR分区：Q4

影响因子：1.5

年份：2023

卷号：12

期号：12

开始页：3744

结束页：3751

文献类型：Article

关键词：Breast cancer; DDB1-and CUL4-associated factor 13 (DCAF13); co-expression network; survival; prognosis

摘要："Background: Breast cancer is one of the main causes of death among women. RNA binding proteins (RBPs) play a crucial role in the progression of breast cancer, with increasingly detailed understanding of RBP functional molecular mechanisms in breast cancer, the functional research of RBPs may help elucidate the potential mechanisms of tumor occurrence, development, invasion, metastasis and prognosis. DDB1-and CUL4-associated factor 13 (DCAF13) is an RBPs has been identified as a substrate receptor for the CUL4-DDB1 E3 ligase complex. Its expression is related to the prognosis of certain cancer. We tried to explore both co-expressed network and biological functions of DCAF13 in breast cancer.Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the different expression of DCAF13 messenger RNA (mRNA) between normal breast tissue and breast carcinoma tissue, and the clinical data about 960 samples were downloaded from the cBio Cancer Genomics Portal (cBioPortal). The expression level of DCAF13, co-expression network, and survival were analyzed. Those with a fold change >= 1 and FDR <0.05 were considered to have statistical significance. Unsupervised clustering of differentially expressed RBPs was performed based on log2-transformed FPKM values using the ""pheatmap"" package in R. Genes with a Spearman score >0.55 were regarded as moderately co-expressed genes. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a co-expression network. Meanwhile, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify the biological process cluster and pathway cluster, respectively.Results: Compared with normal breast tissue, DCAF13 mRNA expression was significantly increased in breast cancer tissue (P<0.01). The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to identify the functions of the co-expressed network. These genes were mainly enriched in mitosis, nuclear division, metabolic process, recombination, replication and repair of DNA, double-strand break repair, posttranscriptional regulation of gene expression, regulation of cell cycle, division and proliferation, regulation of protein stability and also participation in in regulation of poly(A) RNA binding, mRNA binding, tRNA binding, adenosine triphosphate (ATP) binding. KEGG pathway analysis revealed that the genes were mainly enriched in cell cycle, oocyte meiosis and oxidative phosphorylation. According to survival analysis, upregulation of DCAF13 mRNA was significant for overall survival (OS) (P=0.0163).Conclusions: DCAF13 is up-regulated in breast cancer, the OS of patients with DCAF13 up-regulation was obviously reduced. DCAF13 was used as a diagnostic marker and therapeutic target for breast cancer. By building a co-expression network of DCAF13 and conducting bioinformatics analysis, it is possible to find the biomarker to evaluate patient prognosis. This finding provides a new target in mechanism and cell research of breast cancer."

基金机构：Chongqing Natural Science Foundation [cstc-2019jcyj-msxmX0371]; Yongchuan District Technology Innovation and Application Development Project [2023yc-cxfz30007]

基金资助正文："Funding: This study was supported by Chongqing Natural Science Foundation (No. cstc-2019jcyj-msxmX0371) , Yongchuan District Technology Innovation and Application Development Project (No. 2023yc-cxfz30007) ."