Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Urology, Xiang'an Hospital of Xiamen University, Xiamen, China.
Clin Exp Med. 2020 May;20(2):249-259. doi: 10.1007/s10238-019-00604-4. Epub 2020 Jan 24.
Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.
浸润性导管癌(IDC)是最常见的乳腺癌。我们的研究使用基因微阵列数据来选择正常和 IDC 乳腺组织之间差异表达的基因。从这些基因中,我们选择了与肿瘤细胞增殖相关的基因,并将其与 IDC 的已知生物标志物 Ki67 的预后价值进行了比较。对公开可用的基因表达综合数据库(GEO)数据的分析显示,正常组织中有 24 个差异表达基因(DEG),IDC 组织中有 31 个 DEG 用于进一步分析。使用基因芯片分析软件识别 DEG。使用定量 PCR(qPCR)确认 DEG 谱。DEG 功能显示与细胞增殖有关。我们使用免疫组织化学染色在 45 例 IDC 患者中证实了 MCM3 的表达。使用 Kaplan-Meier 生存曲线和 Cox 比例风险回归模型研究了 MCM3 表达与生存之间的关系。在 IDC 和正常组织之间共鉴定出 1307 个差异表达基因,这些基因富集在 32 个基因本体论(GO)术语和 9 个京都基因与基因组百科全书(KEGG)途径中。qPCR 表明 COL1A1 和 MCM3 在 IDC 组织中均显著上调,其中仅 MCM3 与细胞增殖有关。Ki67 与肿瘤分级、ER 状态、PR 状态和 HER2 状态密切相关,而 MCM3 与肿瘤大小、淋巴结和 PR 状态有关。MCM3 与生存之间存在显著关联,但 Ki67 则不然。MCM3 高表达与 IDC 患者预后不良有统计学意义。基因微阵列数据分析的结果证实,MCM3 与细胞增殖反应有关。MCM3 作为一种优于 Ki67 的增殖标志物,代表了一种有价值的独立于 ER 和 HER2 状态的预后工具。