Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes. More mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males.

中文翻译：

---

具有不同代谢谱和女性性别偏见的KDM6A突变频率的非侵入性膀胱癌的基因组亚型。

由于非侵入性疾病的频繁复发，与其他癌症相比，膀胱癌的终生治疗费用更高。对于这一大患者群，需要改善的预后生物标志物和局部治疗。我们定义了Ta期肿瘤的两种主要的基因组亚型。其中之一的特征是9q缺失，包括TSC1，KI67标记指数增加，糖酵解，DNA修复，mTORC1信号转导，未折叠蛋白应答的特征以及胆固醇稳态的改变。与肌肉浸润性膀胱癌突变谱的比较显示，RHOB和染色质修饰基因的总体突变率更低，突变频率更高。女性的非侵袭性肿瘤中组蛋白赖氨酸脱甲基酶KDM6A的突变多于男性。