中性粒细胞胞外陷阱相关结直肠癌肝转移预后特征的建立和 CYP4F3 的表达验证。
Establishment of a neutrophil extracellular trap-related prognostic signature for colorectal cancer liver metastasis and expression validation of CYP4F3.
发表日期:2024 May 25
作者:
Xiao-Li Tang, Zi-Yang Xu, Jiao Guan, Jing Yao, Xiao-Long Tang, Zun-Qiang Zhou, Zheng-Yun Zhang
来源:
GENES & DEVELOPMENT
摘要:
肝转移是结直肠癌 (CRC) 患者死亡的主要原因。中性粒细胞胞外陷阱(NET)成为癌症进展和转移的关键参与者,显示出作为预后生物标志物的前景。我们的目标是制定一个基于中性粒细胞胞外陷阱相关基因的预测模型,并确定对抗 CRLM 的新治疗靶点。我们从基因表达综合 (GEO) 数据库中获取基因表达谱。中性粒细胞胞外陷阱相关基因集从相关文献中获得,并与GEO数据集交叉引用。通过最小绝对收缩和选择算子回归以及随机森林建模进行筛选,鉴定出差异表达基因(DEG),从而建立列线图和亚型分析。随后,对特征基因CYP4F3进行了彻底分析,并通过免疫组织化学染色证实了我们的发现。我们确定了 7 个 DEG(ATG7、CTSG、CYP4F3、F3、IL1B、PDE4B 和 TNF),并建立了 CRLM 发生和预后的列线图。 CYP4F3在CRC和结直肠肝转移(CRLM)中高表达,与CRLM预后呈负相关。它可能作为 CRLM 的潜在治疗靶点。已开发出一种与 NET 相关的新型预后特征,其中 CYP4F3 被确定为 CRLM 的风险因素和潜在目标。© 2024。作者。
Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM.© 2024. The Author(s).