Lower mutant-allele tumor heterogeneity is a biomarker in FGFR3-mutant bladder cancer for better prognosis.
Lower mutant-allele tumor heterogeneity is a biomarker in FGFR3-mutant bladder cancer for better prognosis.
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较低的突变等位基因肿瘤异质性是 FGFR3 突变膀胱癌的生物标志物，可改善预后
DOI：
10.1186/s12957-020-02084-3
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发表时间：
2020-11-26
影响因子：
3.2
通讯作者：
Ji Z
中科院分区：
文献类型：
--
作者：
Han Y;Liu X;Ye H;Tian Y;Ji Z
背景
膀胱癌具有广泛的突变谱和肿瘤内异质性（ITH），这导致了分子表型的差异和对治疗的耐药性。然而，目前没有临床可用的措施来预测使用ITH的患者预后。我们的目的是通过使用ITH建立一个临床相关的生物标志物，用于预测结局。
方法
我们使用Bioconductor R软件包Maftools来有效和全面地分析来自癌症基因组图谱（TCGA）的肌肉浸润性膀胱癌（MIBC）的体细胞变体。然后，我们使用一种多等位基因肿瘤异质性（MATH）算法来测量ITH，并探讨其与临床参数以及突变亚型的相关性。
结果
我们在来自TCGA的MIBC中观察到广泛的体细胞突变。高级别组的MATH值高于低级别组（p 0.05）。较高的MATH值与TP 53突变的存在之间（p = 0.008）以及较低的MATH值与FGFR3突变的存在之间（p = 0.006）存在强相关性。具有FGFR3突变和低MATH值的患者表现出比所有BLCA患者更长的总生存时间（p = 0.044），这在由109名BLCA患者组成的另一膀胱癌数据库中重复。
结论
肿瘤异质性的测量可能是用于识别膀胱癌患者的有用的生物标志物。低MATH值是预测FGFR 3突变患者预后优于所有BLCA患者的独立风险因素。
Background
Bladder cancer displays a broad mutational spectrum and intratumor heterogeneity (ITH), which results in difference in molecular phenotypes and resistance to therapies. However, there are currently no clinically available measures to predict patient prognosis using ITH. We aimed to establish a clinically relevant biomarker by using ITH for informing predictive of outcomes.
Methods
We used the Bioconductor R package Maftools to efficiently and comprehensively analyze somatic variants of muscle-invasive bladder cancer (MIBC) from The Cancer Genome Atlas (TCGA). We then used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters as well as mutational subtypes.
Results
We observed a broad range of somatic mutations in MIBC from TCGA. MATH value was higher for the high-grade group than for the low-grade group (p 0.05). There was a strong correlation between higher MATH value and presence of TP53 mutations (p = 0.008), as well as between lower MATH value and presence of FGFR3 mutations (p = 0.006). Patients with FGFR3 mutation and low MATH value exhibit longer overall survival time than that of all BLCA patients (p = 0.044), which was replicated in another bladder cancer database composed of 109 BLCA patients.
Conclusion
Measures of tumor heterogeneity may be useful biomarkers for identifying patients with bladder cancer. Low MATH value was an independent risk factor that predicted better prognosis for patients with FGFR3 mutation compared to all BLCA patients.
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影响因子：
4.8
作者：
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通讯作者：
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Warrick, Joshua I.;Sjodahl, Gottfrid;DeGraff, David J.
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