Constructing and validating a risk model based on neutrophil-related genes for evaluating prognosis and guiding immunotherapy in colon cancer

作者全名："Wang, Shasha; Wang, Lili; Qiu, Mingxiu; Lin, Zhongkun; Qi, Weiwei; Lv, Jing; Wang, Yan; Lu, Yangyang; Li, Xiaoxuan; Chen, Wenzhi; Qiu, Wensheng"

作者地址："[Wang, Shasha; Chen, Wenzhi; Qiu, Wensheng] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Wang, Shasha; Qi, Weiwei; Lv, Jing; Wang, Yan; Lu, Yangyang; Li, Xiaoxuan; Qiu, Wensheng] Qingdao Univ, Dept Oncol, Affiliated Hosp, Qingdao, Peoples R China; [Wang, Lili] Rizhao Cent Hosp, Dept Oncol, Rizhao, Peoples R China; [Qiu, Mingxiu] Qingdao Municipal Hosp, Dept Resp & Crit Care 2, Qingdao, Peoples R China; [Lin, Zhongkun] Shandong Univ, Shandong Prov Hosp 3, Dept Oncol, Jinan, Peoples R China"

通信作者："Chen, WZ; Qiu, WS (通讯作者)，Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China."

来源：JOURNAL OF GENE MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001202058700001

JCR分区：Q2

影响因子：3.5

年份：2024

卷号：26

期号：4

开始页：　

结束页：　

文献类型：Review

关键词：colon cancer; immunotherapy; neutrophil; nomogram; prognosis

摘要："BackgroundColon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients.MethodsWe first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues.ResultsWe established and validated a risk scoring model based on neutrophil-related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high-risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy.ConclusionsThe low-risk group showed better OS and PFS than the high-risk group in the neutrophil-related gene-based risk model. Patients in the high-risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy. Although immunotherapy is a promising treatment for colon cancer patients, a large proportion of patients do not benefit from immunotherapy. We established and validated a risk scoring model based on neutrophil-related genes and may be more responsive to immunotherapy. image"

基金机构：Qingdao Traditional Chinese Medicine Science and Technology Project

基金资助正文：We gratefully acknowledge the data provided by patients and researchers participating in TCGA.