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Lung Cancer: XPO1突变对转移性非小细胞肺癌(NSCLC)的生存影响

2021-09-10 yd2015 MedSci原创

该研究表明XPO1突变与NSCLC患者较差的预后相关。虽然XPO1突变较罕见,但与治疗的相关性值得今后进一步的探讨。

核蛋白运输是指导重要蛋白质和RNA在细胞核和细胞质之间运输的关键。蛋白质从细胞核的输出主要受Exportin 1 (XPO1)的调控。在癌症中,XPO1普遍过度活跃,可以促进重要的肿瘤抑制因子输出到细胞质。目前,尚无研究评估XPO1在NSCLC中的扩增和突变及其对预后的影响。因此,来自美国研究团队开展了相关研究,评估XPO1扩增或突变对于NSCLC患者的生存影响。相关结果发表在Lung Cancer杂志上。

共18218例NSCLC患者进行研究,发现26例患者伴有XPO1突变(0.14%),24例伴有XPO1扩增。与XPO1野生型肿瘤相比,XPO1突变型肿瘤的TMB较高(79.2% vs. 51.8%, p = 0.007), 而PD-L1水平较低(31.6% vs. 56.3%, p = 0.03),但是XPO1扩增型与XPO1野生型肿瘤之间没有这种相关性。

在XPO1突变的肿瘤中,TP53是最常见的共突变基因,占80%(20/25例)。STK11是第二常见的共突变基因,为26.9% (7 / 26例)。KRAS共突变为19%(n = 5)。EGFR共突变比较罕见(n = 2),未见靶向融合。

         常见共突变基因

在XPO1扩增的肿瘤中,大多数肿瘤TP53阳性,占95.7% (22 / 23例)。第二常见的共同改变是CDKN2A和NFE2L2,均为16.7% (4 / 24例)。

            常见共同的发生基因变化的基因

17449例有完整临床资料,其中有24例XPO1突变。相比较于XPO1野生型患者,XPO1突变型患者的OS较差(HR=1.932; 95% CI: 1.144–3.264; p = 0.012)。而XPO1扩增与预后无明显相关。

           预后

综上,该研究表明XPO1突变与NSCLC患者较差的预后相关。虽然XPO1突变较罕见,但与治疗的相关性值得今后进一步的探讨。

原始出处:

Nagasaka M, Asad MFB, Al Hallak MN, Uddin MH, et al. Impact of XPO1 mutations on survival outcomes in metastatic non-small cell lung cancer (NSCLC). Lung Cancer. 2021 Aug 27;160:92-98. doi: 10.1016/j.lungcan.2021.08.010. Epub ahead of print. PMID: 34482103.

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    2021-09-10 肿肿

    NSCLC下一步突破在于新靶点了,靶向治疗和免疫治疗基本见顶了,再有新的就需要新机制了

    0

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    2021-09-10 查查佳佳

    卡听我解释日本有空了去哪

    0

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