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原发性乳腺癌细胞中的辐射基因表达特征

Radiation Gene-expression Signatures in Primary Breast Cancer Cells.

作者信息

Minafra Luigi, Bravatà Valentina, Cammarata Francesco P, Russo Giorgio, Gilardi Maria C, Forte Giusi I

机构信息

Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Cefalù, Italy.

Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Cefalù, Italy

出版信息

Anticancer Res. 2018 May;38(5):2707-2715. doi: 10.21873/anticanres.12512.

Abstract

BACKGROUND/AIM: In breast cancer (BC) care, radiation therapy (RT) is an efficient treatment to control localized tumor. Radiobiological research is needed to understand molecular differences that affect radiosensitivity of different tumor subtypes and the response variability. The aim of this study was to analyze gene expression profiling (GEP) in primary BC cells following irradiation with doses of 9 Gy and 23 Gy delivered by intraoperative electron radiation therapy (IOERT) in order to define gene signatures of response to high doses of ionizing radiation.

MATERIALS AND METHODS

We performed GEP by cDNA microarrays and evaluated cell survival after IOERT treatment in primary BC cell cultures. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate candidate genes.

RESULTS

We showed, for the first time, a 4-gene and a 6-gene signature, as new molecular biomarkers, in two primary BC cell cultures after exposure at 9 Gy and 23 Gy respectively, for which we observed a significantly high survival rate.

CONCLUSION

Gene signatures activated by different doses of ionizing radiation may predict response to RT and contribute to defining a personalized biological-driven treatment plan.

摘要

背景/目的:在乳腺癌(BC)治疗中,放射治疗(RT)是控制局部肿瘤的有效治疗方法。需要进行放射生物学研究,以了解影响不同肿瘤亚型放射敏感性和反应变异性的分子差异。本研究的目的是分析术中电子放射治疗(IOERT)给予9 Gy和23 Gy剂量照射后原发性BC细胞中的基因表达谱(GEP),以确定对高剂量电离辐射反应的基因特征。

材料与方法

我们通过cDNA微阵列进行GEP,并评估原发性BC细胞培养物中IOERT治疗后的细胞存活情况。进行实时定量逆转录聚合酶链反应(qRT-PCR)以验证候选基因。

结果

我们首次在两种原发性BC细胞培养物中分别暴露于9 Gy和23 Gy后,显示出一个4基因和一个6基因特征,作为新的分子生物标志物,我们观察到其存活率显著较高。

结论

不同剂量电离辐射激活的基因特征可能预测对RT的反应,并有助于制定个性化的生物驱动治疗方案。

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