Nezamivand-Chegini Mahnaz, Kharrati-Koopaee Hamed, Heydari Seyed Taghi, Giahi Hasan, Sabahi Fatemeh, Dehshahri Ali, Bagheri Lankarani Kamran
Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Health Policy Research Center, Institute of Heath, Shiraz University of Medical Sciences, Shiraz, Iran.
Galen Med J. 2023 Jun 26;12:e2598. doi: 10.31661/gmj.v12i.2598. eCollection 2023.
Tamoxifen (TAM) is an effective hormone therapy in order to reduce the risk of cancer recurrence. According to the available findings, TAM contributes to the alterations of genetic variants background and may have role in the effectiveness of treatments via alteration of the genetic variants. The effects of TAM on genomic features were investigated in current study through discovering genetic variants and finding the answer of the following question: "Is there any association between the alterations of genetic variants under TAM consumption and an effective treatment process?"
Whole-transcriptome (RNA-seq) dataset of four investigations including 10 TAM-treated samples and 9 untreated samples as the control groups were derived from European Bioinformatics Institute (EBI). Using the process of variants calling, the differential genetic variants between and gene ontology enrichment analysis were detected through CLC Genomics Workbench (12).
In current study, almost 5.8 million genetic variants were reported. The outcomes of chi-square test showed that distributions of genetic variants between control and treated samples were significant (P0.05). The genetic variants comparison between the control and TAM-treated samples indicated that there were 67 differential genetic variants. Gene ontology enrichment analysis indicated that differential genetic variants were associated with several tumor suppressors and oncogenes such as IL6ST, GEN1, FNTA. HSPA5, NSMCE2, and DDX11.
Most of the candidate genes with differential genetic variants had dual roles as oncogenes or tumor suppressors. Therefore, it can be claimed that TAM has no significant role in an effective treatment through alteration of the genetic variants. In other words, it cannot be concluded that the TAM therapy-resulted alterations of genetic variants have positive or negative roles in the treatment process.
他莫昔芬（TAM）是一种有效的激素疗法，可降低癌症复发风险。根据现有研究结果，TAM会导致基因变异背景的改变，并可能通过改变基因变异在治疗效果中发挥作用。在本研究中，通过发现基因变异并回答以下问题，研究了TAM对基因组特征的影响：“服用TAM时基因变异的改变与有效的治疗过程之间是否存在关联？”
来自欧洲生物信息学研究所（EBI）的四项研究的全转录组（RNA测序）数据集，包括10个TAM治疗样本和9个未治疗样本作为对照组。使用变异检测过程，通过CLC基因组工作台（12）检测差异基因变异和基因本体富集分析。
在本研究中，共报告了近580万个基因变异。卡方检验结果表明，对照样本和治疗样本之间基因变异的分布具有显著性（P<0.05）。对照样本和TAM治疗样本之间的基因变异比较表明，存在67个差异基因变异。基因本体富集分析表明，差异基因变异与几种肿瘤抑制因子和癌基因相关，如IL6ST、GEN1、FNTA、HSPA5、NSMCE2和DDX11。
大多数具有差异基因变异的候选基因具有癌基因或肿瘤抑制因子的双重作用。因此，可以认为TAM通过改变基因变异在有效治疗中没有显著作用。换句话说，不能得出TAM治疗导致的基因变异改变在治疗过程中具有正面或负面作用的结论。
