Yuan Qianqian, Zheng Lewei, Liao Yiqin, Wu Gaosong
Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, China.
World J Surg Oncol. 2021 Mar 23;19(1):86. doi: 10.1186/s12957-021-02200-x.
Triple-negative breast cancer (TNBC) is a major subtype of breast cancer. Due to the lack of effective therapeutic targets, the prognosis is poor. In order to find an effective target, despite many efforts, the molecular mechanisms of TNBC are still not well understood which remain to be a profound clinical challenge.
To identify the candidate genes in the carcinogenesis and progression of TNBC, microarray datasets GSE36693 and GSE65216 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and functional and pathway enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases via DAVID. We constructed the protein-protein interaction network (PPI) and performed the module analysis using STRING and Cytoscape. Then, we reanalyzed the selected DEG genes, and the survival analysis was performed using cBioportal.
A total of 140 DEGs were identified, consisting of 69 upregulated genes and 71 downregulated genes. Three hub genes were upregulated among the selected genes from PPI, and biological process analysis uncovered the fact that these genes were mainly enriched in p53 pathway and the pathways in cancer. Survival analysis showed that only CCNE1 may be involved in the carcinogenesis, invasion, or recurrence of TNBC. The expression levels of CCNE1 were significantly higher in TNBC cells than non-TNBC cells that were detected by qRT-PCR (P < 0.05).
CCNE1 could confer a poorer prognosis in TNBC identified by bioinformatic analysis and plays key roles in the progression of TNBC which may contribute potential targets for the diagnosis, treatment, and prognosis assessment of TNBC.
三阴性乳腺癌（TNBC）是乳腺癌的一种主要亚型。由于缺乏有效的治疗靶点，其预后较差。尽管经过诸多努力，但为了找到一个有效的靶点，TNBC的分子机制仍未被充分理解，这仍是一个严峻的临床挑战。
为了鉴定TNBC发生发展过程中的候选基因，从基因表达综合数据库（GEO）下载了微阵列数据集GSE36693和GSE65216。鉴定差异表达基因（DEGs），并通过DAVID利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）数据库进行功能和通路富集分析。我们构建了蛋白质-蛋白质相互作用网络（PPI），并使用STRING和Cytoscape进行模块分析。然后，我们对选定的DEG基因进行重新分析，并使用cBioportal进行生存分析。
共鉴定出140个DEGs，包括69个上调基因和71个下调基因。在从PPI中选定的基因中，有三个枢纽基因上调，生物学过程分析发现这些基因主要富集于p53通路和癌症相关通路。生存分析表明，只有CCNE1可能参与TNBC的发生、侵袭或复发。通过qRT-PCR检测发现，TNBC细胞中CCNE1的表达水平显著高于非TNBC细胞（P<0.05）。
通过生物信息学分析鉴定出CCNE1可能会导致TNBC预后较差，且在TNBC进展中起关键作用，这可能为TNBC的诊断、治疗和预后评估提供潜在靶点。
