单细胞测序,转录组测序和机器学习的整合,用于构建和验证肝细胞癌中与激素乙化相关的预后风险模型
Yajie Qi1,2, Fulin Wang1,2, Wenchao Ren3
1National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
这项研究使用基因素乙化数据开发了一种11基因肝肝细胞癌 (LIHC) 风险模型. 该模型预测了预后,并将NEU1确定为LIHC的关键治疗标.
科学领域:
- 表观遗传学和癌症基因组学
- 计算生物学和生物信息学
- 瘤学和分子医学的研究.
背景情况:
- 肝肝细胞癌 (LIHC) 是一个严重的临床挑战,预后不佳.
- 激素乙化是一个关键的表观遗传机制,在各种癌症中影响基因表达和瘤进展,但其在LIHC中的作用尚未完全理解.
研究的目的:
- 开发基于与基因素乙化相关的基因的LIHC预测风险模型.
- 调查NEU1作为LIHC潜在生物标志物和治疗点的功能性作用.
主要方法:
- 集成的单细胞/RNA-seq数据与素乙化基因组构建一个LIHC风险模型使用101机器学习算法.
- 评估了模型的预后准确性,免疫格局,化学敏感性,突变特征,铁死和m6A甲基化.
- 通过细胞通信分析,分子对接,体外试验和临床样本验证 (qRT-PCR,WB) 来研究NEU1的功能.
主要成果:
- 一个11基因风险模型 (包括NEU1) 在LIHC队列和亚型中显示出强大的预后准确性.
- 高风险的LIHC患者显示瘤纯度增加,免疫透率降低,对免疫疗法 (PD-L1/L2) 和化疗 (例如,阿克西替尼,西斯普拉丁) 有明显的反应.
- 确定了NEU1作为一个关键的风险因素,可能通过影响内皮细胞通信和分化来促进LIHC进展;NEU1敲击抑制了LIHC细胞生长和瘤进展.
结论:
- 一个基于基因素乙化的新型风险模型有助于LIHC诊断,预后和治疗策略.
- NEU1已成为肝肝细胞癌的重要生物标志物和有前途的治疗点.
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