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鉴定与DNA损伤反应相关的基因作为割抵抗性前列腺癌的生物标志物

Masashi Oshima^1,2,3, Ken-Ichi Takayama¹, Yuta Yamada⁴

¹Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakaecho Itabashi-ku, Tokyo, 173-0015, Japan.

Scientific reports

|November 10, 2023

概括

这项研究确定了6个DNA损伤反应基因,这些基因在抵抗割的前列腺癌 (CRPC) 中被上调. 复制因子C子单元2 (RFC2) 显示了作为前列腺癌预后不佳的生物标志物的潜力.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

激素治疗是前列腺癌 (Pca) 的标准治疗方法,但耐药性导致致命的割抵抗性前列腺癌 (CRPC).
对DNA损伤反应 (DDR) 基因的失调与Pca进展有关.

研究的目的:

为了识别CRPC组织中调高的DDR相关基因.
评估已识别的基因的潜力,特别是RFC2,作为Pca进展和预后的生物标志物.

主要方法:

对良性前列腺,初级Pca和CRPC样本进行RNA测序 (RNA-seq) 分析.
功能分析涉及对CRPC模型单元中的RFC2表达的沉默.
在Pca组织中对RFC2蛋白表达的免疫组织化学 (IHC) 分析.

主要成果:

在CRPC中发现,与Pca.相比,六个DDR相关基因 (RNASEH2A,RFC2,RFC4,LIG1,POLD1,POLE4) 在CRPC中被上调.
沉默RFC2抑制了CRPC细胞增殖,增加了DNA损伤和亡标志物.
高RFC2蛋白表达与Pca预后不佳相关,并且在CRPC组织中升高.

结论:

六个DDR相关的基因在Pca进展中具有重要意义.
RFC2是预测前列腺癌患者不良结果的潜在生物标志物.

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