Eur Urol Oncol:全基因组meta分析发现与非肌层浸润性膀胱癌复发和进展相关的新基因

2021-08-12 AlexYang MedSci原创

非肌层浸润性膀胱癌(NMIBC)的特点是经常复发,并有分期和分级进展的风险。因而需要进一步认识其潜在生物机制。

非肌层浸润性膀胱癌(NMIBC)的特点是经常复发,并有分期和分级进展的风险。因而需要进一步认识其潜在生物机制。

近期,有研究人员鉴定了与NMIBC无复发(RFS)和无进展(PFS)生存相关的单核苷酸多态性(SNPs)

研究人员分析了来自荷兰、英国、加拿大和西班牙的3400名新诊断的NMIBC患者的结果数据,并利用Illumina OmniExpress和Infinium Global Screening Array,结合基因型估算,生成了全基因组种系SNP数据。

研究人员使用了Cox比例风险模型对RFS和PFS进行了队列特异性全基因组关联研究(GWASs)。结果在固定效应的反方差加权元分析中合并。通过功能注释、基因分析、表达定量性状位点分析和转录因子结合位点数据库,研究人员对已鉴定的SNP关联候选基因进行优先排序。之后,在一个独立的NMIBC队列中,测试了优先基因的肿瘤表达水平与RFS和PFS的相关性。

Meta分析显示,第14染色体上存在一个具有全基因组显著意义的RFS相关位点(lead SNP rs12885353, 风险比 [HR] C vs T等位基因为1.55,95%置信区间[CI] 1.33-1.82, p=4.0 × 10-8),包含了基因G2E3和SCFD1。SCFD1的高表达与RFS的增加相关(HR 0.70, 95% CI 0.59-0.84, pFDR=0.003)。另外12个位点显示与RFS也相关(p<10-5),涉及了另外18个候选基因。对于PFS, 10个位点显示出相关性证据,涉及了36个候选基因。其中10个基因的表达水平与PFS具有统计学显著意义,其中4个(IFT140、UBE2I、FAHD1和NME3)与研究人员的meta分析结果和已发表的文献趋势一致。

与RFS相关的位点

综上所述,他们的研究是首次在NMIBC种进行预后的GWAS分析,发现了几个新的候选位点和5个与复发或进展关联的基因

原始出处:

Tessel E Galesloot , Anne J Grotenhuis , Dimitar Kolev et al. Genome-wide Meta-analysis Identifies Novel Genes Associated with Recurrence and Progression in Non-muscle-invasive Bladder Cancer. Eur Urol Oncol. Aug 2021

 

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    2022-01-02 docwu2019
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    2021-12-10 一闲
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    2021-09-13 guojianrong
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    2021-08-13 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

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    2021-08-13 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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