Fu X, Yu G, Guo Y
Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Dec 20;42(12):1822-1831. doi: 10.12122/j.issn.1673-4254.2022.12.10.
To investigate the expression patterns of 19 histone lysine demethylases (KDMs) and their role in bladder cancer.
In this study, UALCAN and GSCALite were used to analyze the transcriptional expression, methylation level and somatic variation of KDMs in bladder cancer samples from TCGA. Kaplan Meier-Plotter and Assistant for clinical bioinformatics were used to investigate the effect of KDMs expression on the prognosis of BLCA samples. The immune infiltration and drug sensitivity of KDMs in bladder cancer were analyzed by Timer and GSCALite.
The KDMs did not show consistent expressions patterns in bladder cancer, where the expressions of KDM1A/1B/2B/4A/4B/5B/5C were significantly upregulated while those of KDM3B/6B/7C were significantly downregulated. Methylation data analysis showed that methylation levels of KDM1A/3B/4A/4B/4C/5A/5B/5C/7B were significantly downregulated and that of KDM7C was upregulated. The transcription levels of 14 KDMs had significant negative correlations with their methylation levels, and among them KDM1A showed the strongest correlation. Mutation analysis revealed that KDM6A had the highest frequency of nonsynonymous mutations with the largest variety, and these mutations were complementary to nonsynonymous mutations of the other KDMs. Survival analysis showed that KDM3A/4C/5D/6A/7B were protective for OS while KDM3B/5B/5C adversely affected RFS of BLCA patients. Further comprehensive prognostic modeling confirmed that KDM4C/6A/7B were potential prognostic biomarkers of bladder cancer, and their expressions were positively correlated with immune infiltration in BLCA patients. KDM2B/3B/4B/4C/5A were negatively correlated with the sensitivity to most anticancer drugs, while KDM2B/4B were positively correlated with the sensitivity to 4 anticancer drugs.
The expression patterns of the KDMs in bladder cancer highlight a high mutation complementarity and a negative correlation between over-expression and hypomethylation level closely related with the prognosis, immune infiltration and drug sensitivity.
研究19种组蛋白赖氨酸去甲基化酶（KDMs）的表达模式及其在膀胱癌中的作用。
在本研究中，使用UALCAN和GSCALite分析来自TCGA的膀胱癌样本中KDMs的转录表达、甲基化水平和体细胞变异。使用Kaplan Meier-Plotter和临床生物信息学助手研究KDMs表达对BLCA样本预后的影响。通过Timer和GSCALite分析膀胱癌中KDMs的免疫浸润和药物敏感性。
KDMs在膀胱癌中未表现出一致的表达模式，其中KDM1A/1B/2B/4A/4B/5B/5C的表达显著上调，而KDM3B/6B/7C的表达显著下调。甲基化数据分析表明，KDM1A/3B/4A/4B/4C/5A/5B/5C/7B的甲基化水平显著下调，而KDM7C的甲基化水平上调。14种KDMs的转录水平与其甲基化水平呈显著负相关，其中KDM1A的相关性最强。突变分析显示，KDM6A的非同义突变频率最高，种类最多，且这些突变与其他KDMs的非同义突变互补。生存分析表明，KDM3A/4C/5D/6A/7B对总生存期有保护作用，而KDM3B/5B/5C对BLCA患者的无复发生存期有不利影响。进一步的综合预后模型证实，KDM4C/6A/7B是膀胱癌潜在的预后生物标志物，其表达与BLCA患者的免疫浸润呈正相关。KDM2B/3B/4B/4C/5A与大多数抗癌药物的敏感性呈负相关，而KDM2B/4B与4种抗癌药物的敏感性呈正相关。
KDMs在膀胱癌中的表达模式突出了高突变互补性以及与预后、免疫浸润和药物敏感性密切相关的过表达与低甲基化水平之间的负相关。
