Identification of genes and miRNAs in paclitaxel treatment for breast cancer

Abstract

Aim

Paclitaxel is a microtubule-stabilizing drug that has therapeutic effect on breast cancer. However, the molecular mechanism of paclitaxel on breast cancer has not been elucidated.

Materials and methods

Microarray data of GSE114403, including 50 pretreatment and 50 posttreatment samples, were downloaded from public database. The differentially expressed genes (DEGs) between pretreatment and posttreatment were identified, followed by functional enrichment analysis. Then, protein–protein interaction (PPI) network and transcription factor (TF)–miRNA–mRNA network were constructed. Finally, the survival analysis of hub genes was performed.

Results

A total of 107 DEGs were screened from pretreatment versus posttreatment. Genes were significantly enriched in GO terms such as inflammatory response, and pathways like cytokine–cytokine receptor interaction pathway. CXCL2, PTGS2, and ATF3 were considered as hub genes in PPI network. TFs such as FOXA2, NFE2L2, as well as miRNAs like has-miR-508-3p and has-miR-584 also played role in the paclitaxel treatment. Additionally, survival analysis revealed that breast cancer patients with high expression level of CXCL2, PTGS2, and ATF3 had longer survival time.

Conclusion

In summary, we demonstrated that CXCL2, PTGS2, and ATF3 might be diagnostic and therapeutic molecular biomarkers for breast cancer. These findings might provide further insights into the pathophysiology of breast cancer, as well as enhance our understanding of the anticancer effects of paclitaxel.

摘要

目的：紫杉醇是一种能够使微管稳定的药物, 对乳腺癌有治疗作用。然而, 紫杉醇对治疗乳腺癌的分子机制尚未阐明。

材料与方法：从公共数据库下载的GSE114403芯片测定的基因数据, 包括50个治疗前和50个治疗后样本的信息。比较治疗前后基因表达的差异, 进行功能富集分析。然后构建蛋白质-蛋白质相互作用（PPI）网络和转录因子-miRNA-mRNA网络。最后进行关键基因的生存分析。

结果：治疗前后共筛选出了107个差异表达的基因。在炎症反应以及细胞因子-细胞因子受体相互作用通路中的基因呈显著富集状态。在蛋白相互作用网络中, CXCL2、PTGS2、ATF3是关键基因。转录因子（FOXA2、NFE2L2）以及miRNAs（has-miR-508-3p、has-miR-584）也在紫杉醇治疗中发挥重要的作用。此外, 生存分析显示CXCL2、PTGS2、ATF3高表达的乳腺癌患者生存时间较长。

结论：总之, 我们的研究表明CXCL2、PTGS2和ATF3可能是乳腺癌诊断和治疗的分子生物标志物。这些发现可能为乳腺癌的病理生理机制提供更多的意见, 并有助于我们对紫杉醇抗肿瘤作用的理解。

Keywords:

• Breast cancer
• paclitaxel treatment
• hub genes
• miRNA
• transcription factor
• bioinformatics analysis

Disclosure statement

No potential conflict of interest was reported by the authors.

Availability of data and materials

Not applicable. This study was only the primary research, and further study has been in progress.

Additional information

Funding

This work was supported by the fund of the National Natural Science Foundation of China with Project No. 11572200, No. 81773043, and No. 31501127; the Shanghai Key Laboratory of Biliary Tract Disease Research Foundation with Project No. 17DZ2260200.