Background/Objectives: It is said that genes that escape from X chromosome inactivation (XCI) contribute to gender differences. We analyzed the prognostic role of these genes and identified a gender-biased difference in prognosis according toKDM6Amutation in the immune therapy cohort (IMvigor 210). We also investigate the gender-biased differential effect ofKDM6Amutation in several public databases of urothelial carcinoma (UC).Methods: We used AACR GENIE, The Cancer Genome Atlas, International Cancer Genome Consortium, several public databases related to immune therapy, chemotherapy, and BCG treatment. We studied the gender-biased prognostic role ofKDM6Amutation in several cohorts and the association betweenKDM6Amutation and immune-related fractions according to gender.Results: The expression ofKDM6Awas higher in females than in males in several cohorts. Mutation ofKDM6Awas observed in about 20–25% of the patients. The rate ofKDM6Amutation was higher in females than in males in several cohorts. Kaplan–Meier analysis revealed a gender-biased difference in prognosis between patients withKDM6Amutations and those with the wild-typeKDM6Ain several cohorts, including the immune therapy cohort. The rate of immune-inflamed type was higher in males than in females in the patients withKDM6Amutation in the IMvigor 210 and UC-GENOME studies. Single-sample Gene Set Enrichment Analysis showed that CD8+ cells and type 1 IFN response fractions and APC co-inhibition fraction were higher in the male than female patients withKDM6Amutation. Similar findings were observed in other immune-related studies (UC-GENOME).Conclusions: The effect ofKDM6Amutation on immune therapy varied according to gender, and the status ofKDM6Amutation may be a promising biomarker in immune therapy in UC.
背景/目的：据称，逃脱X染色体失活（XCI）的基因与性别差异相关。我们分析了这些基因的预后作用，并在免疫治疗队列（IMvigor 210）中根据KDM6A突变识别出预后存在性别偏向性差异。我们还通过多个尿路上皮癌（UC）公共数据库探讨了KDM6A突变的性别偏向性差异效应。 方法：我们使用了AACR GENIE、癌症基因组图谱、国际癌症基因组联盟，以及多个与免疫治疗、化疗和BCG治疗相关的公共数据库。我们研究了多个队列中KDM6A突变的性别偏向性预后作用，以及根据性别KDM6A突变与免疫相关组分之间的关联。 结果：在多个队列中，KDM6A的表达在女性中高于男性。约20–25%的患者中观察到KDM6A突变。在多个队列中，KDM6A突变率在女性中高于男性。Kaplan–Meier分析显示，在包括免疫治疗队列在内的多个队列中，携带KDM6A突变的患者与野生型KDM6A患者之间的预后存在性别偏向性差异。在IMvigor 210和UC-GENOME研究中，携带KDM6A突变的患者中，免疫炎症型比例在男性中高于女性。单样本基因集富集分析显示，在携带KDM6A突变的患者中，CD8+细胞、1型IFN反应组分以及APC共抑制组分在男性中高于女性。其他免疫相关研究（UC-GENOME）中也观察到了类似发现。 结论：KDM6A突变对免疫治疗的影响因性别而异，KDM6A突变状态可能成为尿路上皮癌免疫治疗中一个有前景的生物标志物。
肿瘤(癌症)患者之家