关键词: Colon adenocarcinoma Ferroptosis Neutrophil Transcriptome Tumor immune microenvironment

来  源:   DOI:10.1016/j.heliyon.2024.e33738   PDF(Pubmed)

Abstract:
UNASSIGNED: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive.
UNASSIGNED: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples.
UNASSIGNED: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study.
UNASSIGNED: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.
摘要:
结肠腺癌(COAD)是最常见的恶性肿瘤之一。肿瘤和免疫细胞之间涉及铁凋亡的相互作用在癌症进展中起着至关重要的作用。然而,COAD发展中这种相互作用的生物学基础仍然难以捉摸。
从癌症基因组图谱和国家生物技术信息中心数据库获得COAD样品的转录组数据。采用单样本基因集富集分析,我们计算了每个样本的铁凋亡评分(FS)和免疫细胞浸润水平,利用与铁死亡和各种免疫细胞类型相关的基因的表达水平。FSs大于第75百分位数的样本被归类为高FS亚组,而低于第25百分位数的患者被归类为低FS亚组.此外,从20例结肠患者中收集肿瘤组织样本和邻近的正常组织样本。使用实时定量聚合酶链反应,我们验证了这些样本中某些基因的表达。
具有高FSs的COAD样品经历了良好的生存概率和对抗癌药物的高度敏感性,FSs与病理分期呈负相关。此外,高FS亚组的上调基因在免疫相关通路中表现出富集,表明免疫力和铁中毒之间存在相关性。重要的是,我们发现了一个关键的lncRNA-mRNA共表达网络,该网络连接肿瘤细胞铁性凋亡和免疫浸润(例如,中性粒细胞)在COAD的进展和分类中。进一步的分析确定了几种与铁凋亡相关的lncRNAs(例如,RP11-399O19.9)在此网络内,表明它们在COAD进展中的潜在作用,值得深入研究。
我们的发现为潜在的生物学基础提供了新的见解,特别是涉及到lncRNAs,在COAD和癌症治疗中与铁凋亡相关的基因表达水平。然而,需要进一步的分析和验证以扩大研究结果.
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