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Cancers (Basel):CNGB1作为肌层浸润性膀胱癌新辅助化疗反应的预测因素研究

2021-08-15 AlexYang MedSci原创

基于顺铂的新辅助化疗(NAC)推荐在根治性膀胱切除术之前用于肌层浸润性膀胱癌(MIBC)患者。尽管有5-10%的生存获益,但一些患者没有反应,并会承受大量的毒性后果和延误手术。

基于顺铂的新辅助化疗(NAC)推荐在根治性膀胱切除术之前用于肌层浸润性膀胱癌(MIBC)患者。尽管有5-10%的生存获益,但一些患者没有反应,并会承受大量的毒性后果和延误手术。

到目前为止,还没有临床批准的生物标志物可以预测对NAC的反应,为了更精确地提供治疗,迫切需要鉴定能够临床使用的标志物。

为了解决这个问题,近期,有研究人员对30例MIBC病例进行了机器学习和差异基因表达分析的多方法分析,这些病例是高度选择的,他们对NAC有极强的反应或明显的耐药和/或进展(发现队列)。RGIFE(排序引导的迭代特征消除)机器学习算法已经证明有能力选择具有高预测能力的生物标志物,研究人员利用该方法确定了一个9个基因标记(CNGB1, GGH, HIST1H4F, IDO1, KIF5A, MRPL4, NCDN, PRRT3和SLC35B3)。这些基因能够从非反应者中选择反应者,预测准确率为100%。在使用已发表NAC治疗的MIBC芯片数据进行的元分析中,研究发现的新标记与总生存率相关(验证队列1,n=26,对数等级测试,p=0.02)。另外,与差异基因表达分析相印证,环核苷酸门控通道CNGB1是对NAC无反应者中上调最高的基因。在发现队列的组织微阵列分析中,非反应者的CNGB1免疫染色分数较高(n=30,p=0.02)。对另一个MIBC患者队列(验证队列2,n=99)的Kaplan-Meier分析表明,CNGB1的高水平表达与较短的癌症特异生存期有关(p<0.001)。最后,体外研究显示,siRNA介导的CNGB1敲除增强了MIBC细胞系J82和253JB-V的顺铂敏感性。

CNGB1在NAC非反应者中上调且与MIBC患者的生存有关

综上所述,这些数据揭示了一个新的特征基因集,CNGB1可作为一个更简单的替代来预测MIBC患者化疗敏感性,是非常有前景的生物标志物

原始出处:

Anastasia C Hepburn , Nicola Lazzarini , Rajan Veeratterapillay et al. Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer. Cancers (Basel). Aug 2021

 

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    2021-12-13 anminleiryan
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    2021-08-15 留走人康

    膀胱癌真怪,明明是免疫敏感性肿瘤,为什么PD-1治疗效果不好呢?难道靶点不对?将来CD47会不会有效

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