Hu Dongzhi, Zhou Zhengyang, Wang Junyi, Zhu Kegan
Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Front Mol Biosci. 2022 Sep 20;9:979854. doi: 10.3389/fmolb.2022.979854. eCollection 2022.
Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8 T cells, CD4 T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.
结直肠癌（CRC）仍然是一种常见的消化道恶性肿瘤，在全球范围内发病率和死亡率都很高。目前CRC的临床治疗往往未能取得令人满意的效果。寻找更有效的预测或预后生物标志物，或制定更具针对性的治疗方案，可能有助于改善CRC患者的治疗效果。在此，我们试图研究铁死亡相关基因对CRC预后的影响，并更清楚地表明铁死亡与免疫环境有关。首先，我们从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库中获取了CRC和正常组织的基因表达数据以及相应的临床数据。将差异表达基因（DEGs）与从FerrDb数据库下载的铁死亡相关基因集进行交集分析，得到93个异常表达的铁死亡相关基因。然后，对这些基因进行功能富集分析。进行单因素Cox回归和多因素Cox回归分析，以建立基于铁死亡相关基因的预后模型。在探索预后基因与免疫浸润之间的相关性过程中，我们发现这些基因与CRC中的B细胞、CD8 T细胞、CD4 T细胞、巨噬细胞等细胞密切相关。此外，我们在TCGA-COADREAD中发现了大量的浆细胞和巨噬细胞。最后，建立了一个铁死亡相关基因的预后列线图，包括年龄、性别、分级等预测值。总之，我们建立了基于铁死亡相关基因的结直肠癌（CRC）预后模型，并进一步探索了这些基因与免疫微环境之间的关系。
