Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer.

Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer.
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在非小细胞肺癌中的免疫性和与铁毒相关的基因特征的分子鉴定。

DOI:
10.1186/s12885-021-08541-w
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发表时间:
2021-07-06
期刊:
影响因子:
3.8
通讯作者:
Zhang J
Zhang J
中科院分区:
医学2区
文献类型:
--
作者:
Liu T;Luo H;Zhang J;Hu X;Zhang J

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肺癌是全球癌症相关死亡的主要原因之一。铁凋亡是一种铁依赖性的程序性细胞死亡,在癌症免疫治疗中起着关键作用。然而,免疫和铁蛋白沉积相关基因在非小细胞肺癌(NSCLC)中的作用仍不清楚。从癌症基因组图谱数据集收集与NSCLC有关的RNA-seq数据和临床信息。进行单因素和多因素考克斯回归分析,以确定铁中毒相关基因。建立受试者工作特征(ROC)模型进行敏感性和特异性评价。通过基因本体富集和京都基因百科全书和基因组通路分析,探讨差异表达基因的功能作用。建立了由五个铁中毒相关基因组成的签名,将患者分为高风险和低风险亚组。与低危组患者相比,高危组患者在训练和验证队列中的总生存率显著较差(P < 0.05)。多因素考克斯回归分析显示,危险度评分是影响总生存率的独立因素(P < 0.01)。此外,1个训练队列和2个验证队列的1年、2年和3年ROC分别为0.623 vs. 0.792 vs. 0.635、0.644 vs. 0.792 vs. 0.634和0.631 vs. 0.641 vs. 0.666。功能分析显示,免疫相关通路丰富,并与免疫细胞的异常激活有关。我们确定了五个免疫和铁蛋白沉积相关基因,可能参与非小细胞肺癌的进展和预后。靶向铁凋亡相关基因似乎是NSCLC临床治疗的替代方案。在线版本包含补充材料,可通过10.1186/s12885-021-08541-w获得。
Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC. The online version contains supplementary material available at 10.1186/s12885-021-08541-w.
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