整合了单细胞和批量RNA测序分析,我们识别出了与结肠癌铁死依赖有关的预后标志。
Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer.
发表日期:2023 Aug 04
作者:
Xiaochen Xu, Xinwen Zhang, Qiumei Lin, Yuling Qin, Yihao Liu, Weizhong Tang
来源:
Cell Death & Disease
摘要:
铁质死亡(ferroptosis)是一种依赖于铁和脂质氧化诱导的细胞死亡形式,在包括癌症在内的多种疾病中起着关键作用。由于铁质死亡相关基因(FDRGs)在结直肠癌(CRC)中的预后价值尚不清楚,我们通过全面的单细胞分析来探讨FDRGs在CRC中的重要性。我们下载了GSE161277数据集进行单细胞分析,并为每种细胞类型计算了铁质死亡依赖基因得分(FerrScore)。根据每个细胞类型特定的FerrScore中值,我们将细胞分为低铁质死亡组和高铁质死亡组。通过分析两组之间的差异表达基因,我们识别了FDRGs。我们进一步筛选了这些与预后相关的基因,用于构建一个预后标志,并计算其与免疫浸润的相关性。我们还比较了不同风险组之间的免疫检查点基因疗效,并在结直肠正常细胞系和癌细胞系中进行了定量反转录聚合酶链反应(qRT-PCR)实验,以探索这些标志基因是否可以作为临床预后指标。总共鉴定了523个FDRGs。构建了一个包含五个标志基因的预后标志,将患者分为两个风险组。高风险组的生存率较低,并显示出较高水平的免疫浸润。我们新开发的基于铁质死亡的预后标志对CRC具有很高的预测能力。© 2023. Springer Nature Limited.
Ferroptosis is an iron-dependent form of cell death induced by lipid oxidation with an essential role in diseases, including cancer. Since prognostic value of ferroptosis-dependent related genes (FDRGs) in colorectal cancer (CRC) remains unclear, we explored the significance of FDRGs in CRC through comprehensive single-cell analysis. We downloaded the GSE161277 dataset for single-cell analyses and calculated the ferroptosis-dependent gene score (FerrScore) for each cell type. According to each cell type-specific median FerrScore, we categorized the cells into low- and high-ferroptosis groups. By analyzing differentially-expressed genes across the two groups, we identified FDRGs. We further screened these prognosis-related genes used to develop a prognostic signature and calculated its correlation with immune infiltration. We also compared immune checkpoint gene efficacy among different risk groups, and qRT-PCR was performed in colorectal normal and cancer cell lines to explore whether the signature genes could be used as clinical prognostic indicators. In total, 523 FDRGs were identified. A prognostic signature including five signature genes was constructed, and patients were divided into two risk groups. The high-risk group had poor survival rates and displayed high levels of immune infiltration. Our newly developed ferroptosis-based prognostic signature possessed a high predictive ability for CRC.© 2023. Springer Nature Limited.